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<p class="Title">''Welcome to the Entrainment Simulator!''</p><p class="SubTitle">Presented by [[The Bioclock Studio|http://ccb.ucsd.edu/the-bioclock-studio/index.html]] -- [[Watch our Trailer|https://youtu.be/kc03CDzXOtI]]</p><p class="authors" >//Created 2019, by://</p><p class="authors" style="padding-left:42px;text-indent:-22px;"><span style="color:#223d8e;">//Jiawei Liu, Alisa Kim, Allen Gee, David Welkie, Karen Tonsfeldt, Ben Sheredos, Michael Gorman, and Susan Golden//</span></p><p class="authors" >//Extended 2020, by://</p><p class="authors" style="padding-left:42px;text-indent:-22px;"><span style="color:#223d8e;">//Dan Ly, Lukas Lee, Saisantosh Attaluri, Elizabeth Harrison, Ben Sheredos, Michael Gorman, and Susan Golden//</span></p>
<p>In the real world, the circadian rhythms of humans and other mammals are entrained by their daily light/dark schedules. Humans are diurnal, with most of our activity during daylight hours, whereas some other organisms, such as mice, are nocturnal and therefore most active when it is dark.
In the lab, scientists can use variations of these important environmental cues, such as artificial light/dark schedules, or even just brief pulses of light, to better understand the circadian rhythms of different organisms on a behavioral and molecular level.
In this simulation, you will explore concepts of circadian entrainment and experience what happens when a nocturnal mouse is exposed to varying environments. For example, how will light exposure given at an unexpected time cause the mouse to react? Along the way there will be some helpful questions that will ensure you understand these concepts.</p><p>Ready to <u>[[get started|Review]]</u>?</p><span style="color:#223d8e;">''So, what is entrainment?'' </span>
Entrainment is the coupling of an organism's natural biological rhythm with an environmental rhythm. For example, a nocturnal mouse will couple its wakeful, active phase with the nighttime portion of a 24-hour day/night cycle.
<span style="color:#223d8e;"><u>[[Got it, what's next?|FreeRunning]]</u></span>
<span style="color:#223d8e;">''Free-running'' </span>
When an organism is //not// entrained, we say that it is "free-running." If we take a nocturnal mouse and place it in constant darkness, it will typically have a free-running period (FRP or 𝛕 -- "tau") of around 23.5 hours. That means when the mouse is free-running, the interval between (1) when the mouse wakes up and gets active, goes to sleep, and then (2) wakes up //again// is ''less than'' the 24 hours that make up a normal day. Different species, mouse strains, or individuals have slightly different taus, but they all tend to be close to, but not exactly, 24 h.
Here are two ways to visualize this. (The images below show a short FRP, but not an FRP of exactly 23.5 h). On the left, a circle is shown. This circle is like an everyday clock face, except that it counts off 24 h instead of 12 h. On each successive day, the free-running mouse’s activity begins earlier and earlier: the onset of activity (marked by the line radiating from the center) works its way counter-clockwise around the circle as days unfold. For reference, a second line shows the time of activity onset on the previous day. On the right, an actogram is shown. Each row contains a record of the activity our mouse displays within a 24 h period. Since our mouse has a short free-running period of <24 h, its activity begins earlier and earlier each day: this is visible in the actogram by the way the black bars "drift" to the left.
<img src="http://ccb.ucsd.edu/_images/bioclock/EntrainmentSimulator/01_DialActogramFR.gif">
<span style="color:#223d8e;"><u>[[Proceed: telling circadian time->CT]]</u></span><span style="color:#223d8e;"> ''Let's see how the mouse responds to various acute light pulses'' </span>
<<set $MPArray to [0,0,0,0]>>The mouse will continue to free-run so long as there are no external cues to indicate the time of day. Such external cues, like light, are called ''//Zeitgebers//''. If a Zeitgeber is introduced at the right time, it can shift the mouse's biological rhythms (e.g., as most easily seen in the time of activity onset) to occur earlier or later. This is called a phase shift.
Depending on the __Circadian Time__ at which a light pulse is given, it might induce //either// a phase advance or a phase delay -- or perhaps //neither//. Click on one of the options (A, B, C, or D) to give a single, acute light pulse to the mouse and see what happens.
<div style="max-width: 818px;"><div class="wiggle-container"><div class="wiggle">[["A. CT 0/24"|PulseA][$MPArray[0] to 1]]</div><div class="wiggle">[[B. CT 6|PulseB][$MPArray[1] to 1]]</div><div></div><div class="wiggle">[[C. CT 16|PulseC][$MPArray[2] to 1]]</div><div class="wiggle">[[D. CT 20|PulseD][$MPArray[3] to 1]]</div><div></div></div><img src="http://ccb.ucsd.edu/_images/bioclock/EntrainmentSimulator/03_SubjDayNight.png"></div>
<<if $MPArray is undefined>><<set $MPArray to [1,0,0,0]>><</if>><<set $sum = $MPArray[0]+$MPArray[1]+$MPArray[2]+$MPArray[3]>><span style="color:#c47001;"> ''A. Pulse at CT 0/24: Phase Advance''</span>
An acute light pulse given at the end of subjective night and the beginning of subjective day (e.g., CT 0/24) will produce a modest phase ''advance'', meaning the mouse's next onset of activity occurs ''earlier'' than it would have if the mouse continued free-running.
<div class="hider1 visible">Read the explanation below, then <<link "move on">><<addclass ".hider2" "visible">><<removeclass ".hider1" "visible">><</link>>.
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Click through the images below (using the dots at the top) for an explanation.
<div style="width:100%;"><ul class="slides" style="display:block;"><input type="radio" name="radio-btn" id="img-1" checked /><li class="slide-container"><div class="slide"><img src="http://ccb.ucsd.edu/_images/bioclock/EntrainmentSimulator/05_PulseASlide1.JPG" /><p>''Days 1-5:'' The mouse free-runs as usual with its short FRP. On the left, you can see the end-points of the mouse's activity for the past 5 days. (This is one reason why activity rhythms are commonly double-plotted in actograms, but we are sticking with single-plotting here for simplicity.)</p></div></li><input type="radio" name="radio-btn" id="img-2" /><li class="slide-container"><div class="slide"><img src="http://ccb.ucsd.edu/_images/bioclock/EntrainmentSimulator/05_PulseASlide2.JPG" /><p>''Day 6: ''We apply your selected light pulse at CT 0/24, right at the transition between the subjective night of Day 5 and the subjective morning of Day 6. How will this effect the mouse's activity later on Day 6?
<span style="color:red;">NOTE</span>: In this particular example, on Day 6, CT 0/24 happens to coincide with “0" in the real-world clock time label at the bottom axis of the actogram. But CT time is geared entirely to the subject's rest/activity cycle. When talking about free-running rhythms and circadian time, you can disregard the real-world clock times.
</p></div></li><input type="radio" name="radio-btn" id="img-3" /><li class="slide-container"><div class="slide"><img src="http://ccb.ucsd.edu/_images/bioclock/EntrainmentSimulator/05_PulseASlide3.JPG" /><p>''Day 6:'' The light pulse causes the mouse's activity on Day 6 to begin about an hour earlier than it normally would. That means 1.5 h earlier than the day before — 1 h from the light pulse and 0.5 h from the FRP. On the left, the dotted line indicates when activity would have begun if the mouse were still free-running.</p></div></li><input type="radio" name="radio-btn" id="img-4" /><li class="slide-container"><div class="slide"><img src="http://ccb.ucsd.edu/_images/bioclock/EntrainmentSimulator/05_PulseASlide4.JPG" /><p>''Days 7-24:'' The mouse returns to free-running, but the light pulse has caused every subsequent day's activity to begin earlier. In the actogram, notice how all blocks of activity after Day 6 have shifted to the left. In the circle on the left, the dotted line again indicates when activity would have begun on Day 24 if we had not applied your light pulse.</p>
</div></li>
<li class="nav-dots"><label for="img-1" class="nav-dot" id="img-dot-1"></label><label for="img-2" class="nav-dot" id="img-dot-2"></label><label for="img-3" class="nav-dot" id="img-dot-3"></label><label for="img-4" class="nav-dot" id="img-dot-4"></label></li></ul></div></div><div class="hider2"><<link "Click here to revisit the explanation">><<addclass ".hider1" "visible">><<removeclass ".hider2" "visible">><</link>>, or scroll down to proceed.
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Here's a graphical representation of the effects of the $sum light pulse(s) you've tested so far. Phase advances have a positive value on the y-axis, and phase delays have a negative value on the y-axis.
<<if $MPArray[0] is 1 and $MPArray[1] is 1 and $MPArray[2] is 1 and $MPArray[3] is 1>><div style="max-width:409px;height:auto;margin:auto;"><img src="http://ccb.ucsd.edu/_images/bioclock/EntrainmentSimulator/04_PulseABCD.jpg"></div><</if>><<if $MPArray[0] is 1 and $MPArray[1] is 1 and $MPArray[2] is 1 and $MPArray[3] is 0>><div style="max-width:409px;height:auto;margin:auto;"><img src="http://ccb.ucsd.edu/_images/bioclock/EntrainmentSimulator/04_PulseABC.jpg"></div><</if>><<if $MPArray[0] is 1 and $MPArray[1] is 1 and $MPArray[2] is 0 and $MPArray[3] is 0>><div style="max-width:409px;height:auto;margin:auto;"><img src="http://ccb.ucsd.edu/_images/bioclock/EntrainmentSimulator/04_PulseAB.jpg"></div><</if>><<if $MPArray[0] is 1 and $MPArray[1] is 0 and $MPArray[2] is 0 and $MPArray[3] is 0>><div style="max-width:409px;height:auto;margin:auto;"><img src="http://ccb.ucsd.edu/_images/bioclock/EntrainmentSimulator/04_PulseA.jpg"></div><</if>><<if $MPArray[0] is 1 and $MPArray[1] is 0 and $MPArray[2] is 1 and $MPArray[3] is 0>><div style="max-width:409px;height:auto;margin:auto;"><img src="http://ccb.ucsd.edu/_images/bioclock/EntrainmentSimulator/04_PulseAC.jpg"></div><</if>><<if $MPArray[0] is 1 and $MPArray[1] is 0 and $MPArray[2] is 0 and $MPArray[3] is 1>><div style="max-width:409px;height:auto;margin:auto;"><img src="http://ccb.ucsd.edu/_images/bioclock/EntrainmentSimulator/04_PulseAD.jpg"></div><</if>><<if $MPArray[0] is 1 and $MPArray[1] is 1 and $MPArray[2] is 0 and $MPArray[3] is 1>><div style="max-width:409px;height:auto;margin:auto;"><img src="http://ccb.ucsd.edu/_images/bioclock/EntrainmentSimulator/04_PulseABD.jpg"></div><</if>><<if $MPArray[0] is 1 and $MPArray[1] is 0 and $MPArray[2] is 1 and $MPArray[3] is 1>><div style="max-width:409px;height:auto;margin:auto;"><img src="http://ccb.ucsd.edu/_images/bioclock/EntrainmentSimulator/04_PulseACD.jpg"></div><</if>><<if $MPArray[0] is 0 and $MPArray[1] is 1 and $MPArray[2] is 0 and $MPArray[3] is 0>><div style="max-width:409px;height:auto;margin:auto;"><img src="http://ccb.ucsd.edu/_images/bioclock/EntrainmentSimulator/04_PulseB.jpg"></div><</if>><<if $MPArray[0] is 0 and $MPArray[1] is 1 and $MPArray[2] is 1 and $MPArray[3] is 0>><div style="max-width:409px;height:auto;margin:auto;"><img src="http://ccb.ucsd.edu/_images/bioclock/EntrainmentSimulator/04_PulseBC.jpg"></div><</if>><<if $MPArray[0] is 0 and $MPArray[1] is 1 and $MPArray[2] is 0 and $MPArray[3] is 1>><div style="max-width:409px;height:auto;margin:auto;"><img src="http://ccb.ucsd.edu/_images/bioclock/EntrainmentSimulator/04_PulseBD.jpg"></div><</if>><<if $MPArray[0] is 0 and $MPArray[1] is 1 and $MPArray[2] is 1 and $MPArray[3] is 1>><div style="max-width:409px;height:auto;margin:auto;"><img src="http://ccb.ucsd.edu/_images/bioclock/EntrainmentSimulator/04_PulseBCD.jpg"></div><</if>><<if $MPArray[0] is 0 and $MPArray[1] is 0 and $MPArray[2] is 1 and $MPArray[3] is 0>><div style="max-width:409px;height:auto;margin:auto;"><img src="http://ccb.ucsd.edu/_images/bioclock/EntrainmentSimulator/04_PulseC.jpg"></div><</if>><<if $MPArray[0] is 0 and $MPArray[1] is 0 and $MPArray[2] is 1 and $MPArray[3] is 1>><div style="max-width:409px;height:auto;margin:auto;"><img src="http://ccb.ucsd.edu/_images/bioclock/EntrainmentSimulator/04_PulseCD.jpg"></div><</if>><<if $MPArray[0] is 0 and $MPArray[1] is 0 and $MPArray[2] is 0 and $MPArray[3] is 1>><div style="max-width:409px;height:auto;margin:auto;"><img src="http://ccb.ucsd.edu/_images/bioclock/EntrainmentSimulator/04_PulseD.jpg"></div><</if>>
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<<if $MPArray[0] is 1 and $MPArray[1] is 1 and $MPArray[2] is 1 and $MPArray[3] is 1>> [[That's enough pulses, let's proceed!->PRC]]<</if>><<if $MPArray[0] is 0 or $MPArray[1] is 0 or $MPArray[2] is 0 or $MPArray[3] is 0>>Let's try another pulse!
<div style="max-width: 818px;"><div class="wiggle-container"><<if $MPArray[0] is 0>><div class="wiggle">[["A. CT 0/24"|PulseA][$MPArray[0] to 1]]</div><<elseif $MPArray[0] is 1>><div>==A. CT 0/24==</div><</if>><<if $MPArray[1] is 0>><div class="wiggle">[[B. CT 6|PulseB][$MPArray[1] to 1]]</div><<elseif $MPArray[1] is 1>><div>==B. CT 6==</div><</if>><div></div><<if $MPArray[2] is 0>><div class="wiggle">[[C. CT 16|PulseC][$MPArray[2] to 1]]</div><<elseif $MPArray[2] is 1>><div>==C. CT 16==</div><</if>><<if $MPArray[3] is 0>><div class="wiggle">[[D. CT 20|PulseD][$MPArray[3] to 1]]</div><<elseif $MPArray[3] is 1>><div>==D. CT 20==</div><</if>><div></div></div><img src="http://ccb.ucsd.edu/_images/bioclock/EntrainmentSimulator/03_SubjDayNight.png"></div><</if>></div><<if $MPArray is undefined>><<set $MPArray to [0,1,0,0]>><</if>><<set $sum = $MPArray[0]+$MPArray[1]+$MPArray[2]+$MPArray[3]>><span style="color:#c47001;"> ''B. Pulse at CT 6: No effect!''</span>
An acute light pulse given in the middle of subjective day (e.g., CT6) will not affect the activity of the mouse.
<div class="hider1 visible">Read the explanation below, then <<link "move on">><<addclass ".hider2" "visible">><<removeclass ".hider1" "visible">><</link>>.
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Click through the images below (using the dots at the top) for an explanation.
<div style="width:100%;"><ul class="slides" style="display:block;"><input type="radio" name="radio-btn" id="img-1" checked /><li class="slide-container"><div class="slide"><img src="http://ccb.ucsd.edu/_images/bioclock/EntrainmentSimulator/05_PulseBSlide1.JPG" /><p>''Days 1-5:'' The mouse free-runs as usual with its short FRP. On the left, you can see the end-points of the mouse's activity for the past 5 days. (This is one reason why activity rhythms are commonly double-plotted in actograms, but we are sticking with single-plotting here for simplicity.)</p></div></li><input type="radio" name="radio-btn" id="img-2" /><li class="slide-container"><div class="slide"><img src="http://ccb.ucsd.edu/_images/bioclock/EntrainmentSimulator/05_PulseBSlide2.JPG" /><p>''Day 6: '' We apply your selected light pulse at CT 6, right in the middle of subjective day. How will this effect the mouse's activity later on Day 6?
<span style="color:red;">NOTE</span>: In this particular example, on Day 6, CT 6 happens to coincide with “6" in the real-world clock time label at the bottom axis of the actogram. But CT time is geared entirely to the subject's rest/activity cycle. When talking about free-running rhythms and circadian time, you can disregard the real-world clock times.</p></div></li><input type="radio" name="radio-btn" id="img-3" /><li class="slide-container"><div class="slide"><img src="http://ccb.ucsd.edu/_images/bioclock/EntrainmentSimulator/05_PulseBSlide3.JPG" /><p>''Day 6:'' The light pulse has no effect on the mouse's onset of activity. Think of it this way: your light pulse occurs in the middle of subjective day, when the mouse's clock already "thinks" that there //should// be light, so no adjustment is made.</p><p><span style="color:red;">''Note:''</span> Although the mouse's activity on Day 6 does begin 0.5 h earlier than it did on Day 5, this is NOT evidence of a phase shift. It is just a short free-running period. A phase shift is a one-time response to a Zeitgeber that causes the entire cycle of activity and rest to occur earlier (advance) or later (delay) than it would have otherwise.</p></div></li><input type="radio" name="radio-btn" id="img-4" /><li class="slide-container"><div class="slide"><img src="http://ccb.ucsd.edu/_images/bioclock/EntrainmentSimulator/05_PulseBSlide4.JPG" /><p>''Days 7-24:'' The mouse continues free-running. Despite the light pulse, the onset of activity each day occurs a half hour earlier than the day before, reflecting the mouse's natural short FRP of 23.5 h.</p>
</div></li>
<li class="nav-dots"><label for="img-1" class="nav-dot" id="img-dot-1"></label><label for="img-2" class="nav-dot" id="img-dot-2"></label><label for="img-3" class="nav-dot" id="img-dot-3"></label><label for="img-4" class="nav-dot" id="img-dot-4"></label></li></ul></div></div><div class="hider2"><<link "Click here to revisit the explanation">><<addclass ".hider1" "visible">><<removeclass ".hider2" "visible">><</link>>, or scroll down to proceed.
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Here's a graphical representation of the effects of the $sum light pulse(s) you've tested so far. Phase advances have a positive value on the y-axis, and phase delays have a negative value on the y-axis.
<<if $MPArray[0] is 1 and $MPArray[1] is 1 and $MPArray[2] is 1 and $MPArray[3] is 1>><div style="max-width:409px;height:auto;margin:auto;"><img src="http://ccb.ucsd.edu/_images/bioclock/EntrainmentSimulator/04_PulseABCD.jpg"></div><</if>><<if $MPArray[0] is 1 and $MPArray[1] is 1 and $MPArray[2] is 1 and $MPArray[3] is 0>><div style="max-width:409px;height:auto;margin:auto;"><img src="http://ccb.ucsd.edu/_images/bioclock/EntrainmentSimulator/04_PulseABC.jpg"></div><</if>><<if $MPArray[0] is 1 and $MPArray[1] is 1 and $MPArray[2] is 0 and $MPArray[3] is 0>><div style="max-width:409px;height:auto;margin:auto;"><img src="http://ccb.ucsd.edu/_images/bioclock/EntrainmentSimulator/04_PulseAB.jpg"></div><</if>><<if $MPArray[0] is 1 and $MPArray[1] is 0 and $MPArray[2] is 0 and $MPArray[3] is 0>><div style="max-width:409px;height:auto;margin:auto;"><img src="http://ccb.ucsd.edu/_images/bioclock/EntrainmentSimulator/04_PulseA.jpg"></div><</if>><<if $MPArray[0] is 1 and $MPArray[1] is 0 and $MPArray[2] is 1 and $MPArray[3] is 0>><div style="max-width:409px;height:auto;margin:auto;"><img src="http://ccb.ucsd.edu/_images/bioclock/EntrainmentSimulator/04_PulseAC.jpg"></div><</if>><<if $MPArray[0] is 1 and $MPArray[1] is 0 and $MPArray[2] is 0 and $MPArray[3] is 1>><div style="max-width:409px;height:auto;margin:auto;"><img src="http://ccb.ucsd.edu/_images/bioclock/EntrainmentSimulator/04_PulseAD.jpg"></div><</if>><<if $MPArray[0] is 1 and $MPArray[1] is 1 and $MPArray[2] is 0 and $MPArray[3] is 1>><div style="max-width:409px;height:auto;margin:auto;"><img src="http://ccb.ucsd.edu/_images/bioclock/EntrainmentSimulator/04_PulseABD.jpg"></div><</if>><<if $MPArray[0] is 1 and $MPArray[1] is 0 and $MPArray[2] is 1 and $MPArray[3] is 1>><div style="max-width:409px;height:auto;margin:auto;"><img src="http://ccb.ucsd.edu/_images/bioclock/EntrainmentSimulator/04_PulseACD.jpg"></div><</if>><<if $MPArray[0] is 0 and $MPArray[1] is 1 and $MPArray[2] is 0 and $MPArray[3] is 0>><div style="max-width:409px;height:auto;margin:auto;"><img src="http://ccb.ucsd.edu/_images/bioclock/EntrainmentSimulator/04_PulseB.jpg"></div><</if>><<if $MPArray[0] is 0 and $MPArray[1] is 1 and $MPArray[2] is 1 and $MPArray[3] is 0>><div style="max-width:409px;height:auto;margin:auto;"><img src="http://ccb.ucsd.edu/_images/bioclock/EntrainmentSimulator/04_PulseBC.jpg"></div><</if>><<if $MPArray[0] is 0 and $MPArray[1] is 1 and $MPArray[2] is 0 and $MPArray[3] is 1>><div style="max-width:409px;height:auto;margin:auto;"><img src="http://ccb.ucsd.edu/_images/bioclock/EntrainmentSimulator/04_PulseBD.jpg"></div><</if>><<if $MPArray[0] is 0 and $MPArray[1] is 1 and $MPArray[2] is 1 and $MPArray[3] is 1>><div style="max-width:409px;height:auto;margin:auto;"><img src="http://ccb.ucsd.edu/_images/bioclock/EntrainmentSimulator/04_PulseBCD.jpg"></div><</if>><<if $MPArray[0] is 0 and $MPArray[1] is 0 and $MPArray[2] is 1 and $MPArray[3] is 0>><div style="max-width:409px;height:auto;margin:auto;"><img src="http://ccb.ucsd.edu/_images/bioclock/EntrainmentSimulator/04_PulseC.jpg"></div><</if>><<if $MPArray[0] is 0 and $MPArray[1] is 0 and $MPArray[2] is 1 and $MPArray[3] is 1>><div style="max-width:409px;height:auto;margin:auto;"><img src="http://ccb.ucsd.edu/_images/bioclock/EntrainmentSimulator/04_PulseCD.jpg"></div><</if>><<if $MPArray[0] is 0 and $MPArray[1] is 0 and $MPArray[2] is 0 and $MPArray[3] is 1>><div style="max-width:409px;height:auto;margin:auto;"><img src="http://ccb.ucsd.edu/_images/bioclock/EntrainmentSimulator/04_PulseD.jpg"></div><</if>>
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<<if $MPArray[0] is 1 and $MPArray[1] is 1 and $MPArray[2] is 1 and $MPArray[3] is 1>> [[That's enough pulses, let's proceed!->PRC]]<</if>><<if $MPArray[0] is 0 or $MPArray[1] is 0 or $MPArray[2] is 0 or $MPArray[3] is 0>>Let's try another pulse!
<div style="max-width: 818px;"><div class="wiggle-container"><<if $MPArray[0] is 0>><div class="wiggle">[["A. CT 0/24"|PulseA][$MPArray[0] to 1]]</div><<elseif $MPArray[0] is 1>><div>==A. CT 0/24==</div><</if>><<if $MPArray[1] is 0>><div class="wiggle">[[B. CT 6|PulseB][$MPArray[1] to 1]]</div><<elseif $MPArray[1] is 1>><div>==B. CT 6==</div><</if>><div></div><<if $MPArray[2] is 0>><div class="wiggle">[[C. CT 16|PulseC][$MPArray[2] to 1]]</div><<elseif $MPArray[2] is 1>><div>==C. CT 16==</div><</if>><<if $MPArray[3] is 0>><div class="wiggle">[[D. CT 20|PulseD][$MPArray[3] to 1]]</div><<elseif $MPArray[3] is 1>><div>==D. CT 20==</div><</if>><div></div></div><img src="http://ccb.ucsd.edu/_images/bioclock/EntrainmentSimulator/03_SubjDayNight.png"></div><</if>></div><<if $MPArray is undefined>><<set $MPArray to [0,0,1,0]>><</if>><<set $sum = $MPArray[0]+$MPArray[1]+$MPArray[2]+$MPArray[3]>><span style="color:#c47001;"> ''C. Pulse at CT 16: Phase Delay''</span>
An acute light pulse given in early subjective night (e.g., CT 16) will produce a phase ''delay'', meaning the mouse's next onset of activity occurs ''later'' than it would have if the mouse continued free-running.
<div class="hider1 visible">Read the explanation below, then <<link "move on">><<addclass ".hider2" "visible">><<removeclass ".hider1" "visible">><</link>>.
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Click through the images below (using the dots at the top) for an explanation.
<div style="width:100%;"><ul class="slides" style="display:block;"><input type="radio" name="radio-btn" id="img-1" checked /><li class="slide-container"><div class="slide"><img src="http://ccb.ucsd.edu/_images/bioclock/EntrainmentSimulator/05_PulseCSlide1.JPG" /><p>''Days 1-5:'' The mouse free-runs as usual with its short FRP. On the left, you can see the end-points of the mouse's activity for the past 5 days. (This is one reason why activity rhythms are commonly double-plotted in actograms, but we are sticking with single-plotting here for simplicity.)</p></div></li><input type="radio" name="radio-btn" id="img-2" /><li class="slide-container"><div class="slide"><img src="http://ccb.ucsd.edu/_images/bioclock/EntrainmentSimulator/05_PulseCSlide2.JPG" /><p>''Day 6: ''We apply your selected light pulse at CT 16, about 1/3 of the way through subjective night. How will this effect the mouse's activity on Day 7?
<span style="color:red;">NOTE</span>: In this particular example, on Day 6, CT 16 happens to coincide with “16" in the real-world clock time label at the bottom axis of the actogram. But CT time is geared entirely to the subject's rest/activity cycle. When talking about free-running rhythms and circadian time, you can disregard the real-world clock times.</p></div></li><input type="radio" name="radio-btn" id="img-3" /><li class="slide-container"><div class="slide"><img src="http://ccb.ucsd.edu/_images/bioclock/EntrainmentSimulator/05_PulseCSlide3.JPG" /><p>''Day 7:'' The light pulse causes the mouse's daily activity to begin about 3.5 h later than it normally would. On the left, the dotted line indicates when activity would have begun if the mouse were still free-running.</p></div></li><input type="radio" name="radio-btn" id="img-4" /><li class="slide-container"><div class="slide"><img src="http://ccb.ucsd.edu/_images/bioclock/EntrainmentSimulator/05_PulseCSlide4.JPG" /><p>''Days 8-24:'' The mouse returns to free-running, but the light pulse has caused every subsequent day's activity to begin later. In the actogram, notice how all blocks of activity after Day 7 have shifted to the right. In the circle on the left, the dotted line again indicates when activity would have begun on Day 24 if we had not applied your light pulse.</p>
</div></li>
<li class="nav-dots"><label for="img-1" class="nav-dot" id="img-dot-1"></label><label for="img-2" class="nav-dot" id="img-dot-2"></label><label for="img-3" class="nav-dot" id="img-dot-3"></label><label for="img-4" class="nav-dot" id="img-dot-4"></label></li></ul></div></div><div class="hider2"><<link "Click here to revisit the explanation">><<addclass ".hider1" "visible">><<removeclass ".hider2" "visible">><</link>>, or scroll down to proceed.
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Here's a graphical representation of the effects of the $sum light pulse(s) you've tested so far. Phase advances have a positive value on the y-axis, and phase delays have a negative value on the y-axis.
<<if $MPArray[0] is 1 and $MPArray[1] is 1 and $MPArray[2] is 1 and $MPArray[3] is 1>><div style="max-width:409px;height:auto;margin:auto;"><img src="http://ccb.ucsd.edu/_images/bioclock/EntrainmentSimulator/04_PulseABCD.jpg"></div><</if>><<if $MPArray[0] is 1 and $MPArray[1] is 1 and $MPArray[2] is 1 and $MPArray[3] is 0>><div style="max-width:409px;height:auto;margin:auto;"><img src="http://ccb.ucsd.edu/_images/bioclock/EntrainmentSimulator/04_PulseABC.jpg"></div><</if>><<if $MPArray[0] is 1 and $MPArray[1] is 1 and $MPArray[2] is 0 and $MPArray[3] is 0>><div style="max-width:409px;height:auto;margin:auto;"><img src="http://ccb.ucsd.edu/_images/bioclock/EntrainmentSimulator/04_PulseAB.jpg"></div><</if>><<if $MPArray[0] is 1 and $MPArray[1] is 0 and $MPArray[2] is 0 and $MPArray[3] is 0>><div style="max-width:409px;height:auto;margin:auto;"><img src="http://ccb.ucsd.edu/_images/bioclock/EntrainmentSimulator/04_PulseA.jpg"></div><</if>><<if $MPArray[0] is 1 and $MPArray[1] is 0 and $MPArray[2] is 1 and $MPArray[3] is 0>><div style="max-width:409px;height:auto;margin:auto;"><img src="http://ccb.ucsd.edu/_images/bioclock/EntrainmentSimulator/04_PulseAC.jpg"></div><</if>><<if $MPArray[0] is 1 and $MPArray[1] is 0 and $MPArray[2] is 0 and $MPArray[3] is 1>><div style="max-width:409px;height:auto;margin:auto;"><img src="http://ccb.ucsd.edu/_images/bioclock/EntrainmentSimulator/04_PulseAD.jpg"></div><</if>><<if $MPArray[0] is 1 and $MPArray[1] is 1 and $MPArray[2] is 0 and $MPArray[3] is 1>><div style="max-width:409px;height:auto;margin:auto;"><img src="http://ccb.ucsd.edu/_images/bioclock/EntrainmentSimulator/04_PulseABD.jpg"></div><</if>><<if $MPArray[0] is 1 and $MPArray[1] is 0 and $MPArray[2] is 1 and $MPArray[3] is 1>><div style="max-width:409px;height:auto;margin:auto;"><img src="http://ccb.ucsd.edu/_images/bioclock/EntrainmentSimulator/04_PulseACD.jpg"></div><</if>><<if $MPArray[0] is 0 and $MPArray[1] is 1 and $MPArray[2] is 0 and $MPArray[3] is 0>><div style="max-width:409px;height:auto;margin:auto;"><img src="http://ccb.ucsd.edu/_images/bioclock/EntrainmentSimulator/04_PulseB.jpg"></div><</if>><<if $MPArray[0] is 0 and $MPArray[1] is 1 and $MPArray[2] is 1 and $MPArray[3] is 0>><div style="max-width:409px;height:auto;margin:auto;"><img src="http://ccb.ucsd.edu/_images/bioclock/EntrainmentSimulator/04_PulseBC.jpg"></div><</if>><<if $MPArray[0] is 0 and $MPArray[1] is 1 and $MPArray[2] is 0 and $MPArray[3] is 1>><div style="max-width:409px;height:auto;margin:auto;"><img src="http://ccb.ucsd.edu/_images/bioclock/EntrainmentSimulator/04_PulseBD.jpg"></div><</if>><<if $MPArray[0] is 0 and $MPArray[1] is 1 and $MPArray[2] is 1 and $MPArray[3] is 1>><div style="max-width:409px;height:auto;margin:auto;"><img src="http://ccb.ucsd.edu/_images/bioclock/EntrainmentSimulator/04_PulseBCD.jpg"></div><</if>><<if $MPArray[0] is 0 and $MPArray[1] is 0 and $MPArray[2] is 1 and $MPArray[3] is 0>><div style="max-width:409px;height:auto;margin:auto;"><img src="http://ccb.ucsd.edu/_images/bioclock/EntrainmentSimulator/04_PulseC.jpg"></div><</if>><<if $MPArray[0] is 0 and $MPArray[1] is 0 and $MPArray[2] is 1 and $MPArray[3] is 1>><div style="max-width:409px;height:auto;margin:auto;"><img src="http://ccb.ucsd.edu/_images/bioclock/EntrainmentSimulator/04_PulseCD.jpg"></div><</if>><<if $MPArray[0] is 0 and $MPArray[1] is 0 and $MPArray[2] is 0 and $MPArray[3] is 1>><div style="max-width:409px;height:auto;margin:auto;"><img src="http://ccb.ucsd.edu/_images/bioclock/EntrainmentSimulator/04_PulseD.jpg"></div><</if>>
----
<<if $MPArray[0] is 1 and $MPArray[1] is 1 and $MPArray[2] is 1 and $MPArray[3] is 1>> [[That's enough pulses, let's proceed!->PRC]]<</if>><<if $MPArray[0] is 0 or $MPArray[1] is 0 or $MPArray[2] is 0 or $MPArray[3] is 0>>Let's try another pulse!
<div style="max-width: 818px;"><div class="wiggle-container"><<if $MPArray[0] is 0>><div class="wiggle">[["A. CT 0/24"|PulseA][$MPArray[0] to 1]]</div><<elseif $MPArray[0] is 1>><div>==A. CT 0/24==</div><</if>><<if $MPArray[1] is 0>><div class="wiggle">[[B. CT 6|PulseB][$MPArray[1] to 1]]</div><<elseif $MPArray[1] is 1>><div>==B. CT 6==</div><</if>><div></div><<if $MPArray[2] is 0>><div class="wiggle">[[C. CT 16|PulseC][$MPArray[2] to 1]]</div><<elseif $MPArray[2] is 1>><div>==C. CT 16==</div><</if>><<if $MPArray[3] is 0>><div class="wiggle">[[D. CT 20|PulseD][$MPArray[3] to 1]]</div><<elseif $MPArray[3] is 1>><div>==D. CT 20==</div><</if>><div></div></div><img src="http://ccb.ucsd.edu/_images/bioclock/EntrainmentSimulator/03_SubjDayNight.png"></div><</if>></div><<if $MPArray is undefined>><<set $MPArray to [0,0,0,1]>><</if>><<set $sum = $MPArray[0]+$MPArray[1]+$MPArray[2]+$MPArray[3]>><span style="color:#c47001;"> ''D. Pulse at CT 20: Phase Advance''</span>
An acute light pulse given in late subjective night (e.g., CT 20) can produce a large phase ''advance'', meaning the mouse's next onset of activity occurs ''earlier'' than it would have if the mouse continued free-running.
<div class="hider1 visible">Read the explanation below, then <<link "move on">><<addclass ".hider2" "visible">><<removeclass ".hider1" "visible">><</link>>.
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Click through the images below (using the dots at the top) for an explanation.
<div style="width:100%;"><ul class="slides" style="display:block;"><input type="radio" name="radio-btn" id="img-1" checked /><li class="slide-container"><div class="slide"><img src="http://ccb.ucsd.edu/_images/bioclock/EntrainmentSimulator/05_PulseDSlide1.JPG" /><p>''Days 1-5:'' The mouse free-runs as usual with its short FRP. On the left, you can see the end-points of the mouse's activity for the past 5 days. (This is one reason why activity rhythms are commonly double-plotted in actograms, but we are sticking with single-plotting here for simplicity.)</p></div></li><input type="radio" name="radio-btn" id="img-2" /><li class="slide-container"><div class="slide"><img src="http://ccb.ucsd.edu/_images/bioclock/EntrainmentSimulator/05_PulseDSlide2.JPG" /><p>''Day 6: ''We apply your selected light pulse at CT 20, near the end of subjective night. How will this effect the mouse's activity on Day 7?
<span style="color:red;">NOTE</span>: In this particular example, on Day 6, CT 20 happens to coincide with “20" in the real-world clock time label at the bottom axis of the actogram. But CT time is geared entirely to the subject's rest/activity cycle. When talking about free-running rhythms and circadian time, you can disregard the real-world clock times.</p></div></li><input type="radio" name="radio-btn" id="img-3" /><li class="slide-container"><div class="slide"><img src="http://ccb.ucsd.edu/_images/bioclock/EntrainmentSimulator/05_PulseDSlide3.JPG" /><p>''Day 7:'' The light pulse causes the mouse's daily activity to begin about 2 h earlier than it normally would. Because FRP is 23.5 h, that means the next onset is 2.5 h earlier than the day. On the left, the dotted line indicates when activity would have begun if the mouse were still free-running.</p></div></li><input type="radio" name="radio-btn" id="img-4" /><li class="slide-container"><div class="slide"><img src="http://ccb.ucsd.edu/_images/bioclock/EntrainmentSimulator/05_PulseDSlide4.JPG" /><p>''Days 8-24:'' The mouse returns to free-running, but the light pulse has caused every subsequent day's activity to begin earlier. In the actogram, notice how all blocks of activity after Day 7 have shifted to the left. In the circle on the left, the dotted line again indicates when activity would have begun on Day 24 if we had not applied your light pulse.</p>
</div></li>
<li class="nav-dots"><label for="img-1" class="nav-dot" id="img-dot-1"></label><label for="img-2" class="nav-dot" id="img-dot-2"></label><label for="img-3" class="nav-dot" id="img-dot-3"></label><label for="img-4" class="nav-dot" id="img-dot-4"></label></li></ul></div></div><div class="hider2"><<link "Click here to revisit the explanation">><<addclass ".hider1" "visible">><<removeclass ".hider2" "visible">><</link>>, or scroll down to proceed.
----
Here's a graphical representation of the effects of the $sum light pulse(s) you've tested so far. Phase advances have a positive value on the y-axis, and phase delays have a negative value on the y-axis.
<<if $MPArray[0] is 1 and $MPArray[1] is 1 and $MPArray[2] is 1 and $MPArray[3] is 1>><div style="max-width:409px;height:auto;margin:auto;"><img src="http://ccb.ucsd.edu/_images/bioclock/EntrainmentSimulator/04_PulseABCD.jpg"></div><</if>><<if $MPArray[0] is 1 and $MPArray[1] is 1 and $MPArray[2] is 1 and $MPArray[3] is 0>><div style="max-width:409px;height:auto;margin:auto;"><img src="http://ccb.ucsd.edu/_images/bioclock/EntrainmentSimulator/04_PulseABC.jpg"></div><</if>><<if $MPArray[0] is 1 and $MPArray[1] is 1 and $MPArray[2] is 0 and $MPArray[3] is 0>><div style="max-width:409px;height:auto;margin:auto;"><img src="http://ccb.ucsd.edu/_images/bioclock/EntrainmentSimulator/04_PulseAB.jpg"></div><</if>><<if $MPArray[0] is 1 and $MPArray[1] is 0 and $MPArray[2] is 0 and $MPArray[3] is 0>><div style="max-width:409px;height:auto;margin:auto;"><img src="http://ccb.ucsd.edu/_images/bioclock/EntrainmentSimulator/04_PulseA.jpg"></div><</if>><<if $MPArray[0] is 1 and $MPArray[1] is 0 and $MPArray[2] is 1 and $MPArray[3] is 0>><div style="max-width:409px;height:auto;margin:auto;"><img src="http://ccb.ucsd.edu/_images/bioclock/EntrainmentSimulator/04_PulseAC.jpg"></div><</if>><<if $MPArray[0] is 1 and $MPArray[1] is 0 and $MPArray[2] is 0 and $MPArray[3] is 1>><div style="max-width:409px;height:auto;margin:auto;"><img src="http://ccb.ucsd.edu/_images/bioclock/EntrainmentSimulator/04_PulseAD.jpg"></div><</if>><<if $MPArray[0] is 1 and $MPArray[1] is 1 and $MPArray[2] is 0 and $MPArray[3] is 1>><div style="max-width:409px;height:auto;margin:auto;"><img src="http://ccb.ucsd.edu/_images/bioclock/EntrainmentSimulator/04_PulseABD.jpg"></div><</if>><<if $MPArray[0] is 1 and $MPArray[1] is 0 and $MPArray[2] is 1 and $MPArray[3] is 1>><div style="max-width:409px;height:auto;margin:auto;"><img src="http://ccb.ucsd.edu/_images/bioclock/EntrainmentSimulator/04_PulseACD.jpg"></div><</if>><<if $MPArray[0] is 0 and $MPArray[1] is 1 and $MPArray[2] is 0 and $MPArray[3] is 0>><div style="max-width:409px;height:auto;margin:auto;"><img src="http://ccb.ucsd.edu/_images/bioclock/EntrainmentSimulator/04_PulseB.jpg"></div><</if>><<if $MPArray[0] is 0 and $MPArray[1] is 1 and $MPArray[2] is 1 and $MPArray[3] is 0>><div style="max-width:409px;height:auto;margin:auto;"><img src="http://ccb.ucsd.edu/_images/bioclock/EntrainmentSimulator/04_PulseBC.jpg"></div><</if>><<if $MPArray[0] is 0 and $MPArray[1] is 1 and $MPArray[2] is 0 and $MPArray[3] is 1>><div style="max-width:409px;height:auto;margin:auto;"><img src="http://ccb.ucsd.edu/_images/bioclock/EntrainmentSimulator/04_PulseBD.jpg"></div><</if>><<if $MPArray[0] is 0 and $MPArray[1] is 1 and $MPArray[2] is 1 and $MPArray[3] is 1>><div style="max-width:409px;height:auto;margin:auto;"><img src="http://ccb.ucsd.edu/_images/bioclock/EntrainmentSimulator/04_PulseBCD.jpg"></div><</if>><<if $MPArray[0] is 0 and $MPArray[1] is 0 and $MPArray[2] is 1 and $MPArray[3] is 0>><div style="max-width:409px;height:auto;margin:auto;"><img src="http://ccb.ucsd.edu/_images/bioclock/EntrainmentSimulator/04_PulseC.jpg"></div><</if>><<if $MPArray[0] is 0 and $MPArray[1] is 0 and $MPArray[2] is 1 and $MPArray[3] is 1>><div style="max-width:409px;height:auto;margin:auto;"><img src="http://ccb.ucsd.edu/_images/bioclock/EntrainmentSimulator/04_PulseCD.jpg"></div><</if>><<if $MPArray[0] is 0 and $MPArray[1] is 0 and $MPArray[2] is 0 and $MPArray[3] is 1>><div style="max-width:409px;height:auto;margin:auto;"><img src="http://ccb.ucsd.edu/_images/bioclock/EntrainmentSimulator/04_PulseD.jpg"></div><</if>>
----
<<if $MPArray[0] is 1 and $MPArray[1] is 1 and $MPArray[2] is 1 and $MPArray[3] is 1>> [[That's enough pulses, let's proceed!->PRC]]<</if>><<if $MPArray[0] is 0 or $MPArray[1] is 0 or $MPArray[2] is 0 or $MPArray[3] is 0>>Let's try another pulse!
<div style="max-width: 818px;"><div class="wiggle-container"><<if $MPArray[0] is 0>><div class="wiggle">[["A. CT 0/24"|PulseA][$MPArray[0] to 1]]</div><<elseif $MPArray[0] is 1>><div>==A. CT 0/24==</div><</if>><<if $MPArray[1] is 0>><div class="wiggle">[[B. CT 6|PulseB][$MPArray[1] to 1]]</div><<elseif $MPArray[1] is 1>><div>==B. CT 6==</div><</if>><div></div><<if $MPArray[2] is 0>><div class="wiggle">[[C. CT 16|PulseC][$MPArray[2] to 1]]</div><<elseif $MPArray[2] is 1>><div>==C. CT 16==</div><</if>><<if $MPArray[3] is 0>><div class="wiggle">[[D. CT 20|PulseD][$MPArray[3] to 1]]</div><<elseif $MPArray[3] is 1>><div>==D. CT 20==</div><</if>><div></div></div><img src="http://ccb.ucsd.edu/_images/bioclock/EntrainmentSimulator/03_SubjDayNight.png"></div><</if>></div><span style="color:#223d8e;"> ''The Phase Response Curve (PRC)''</span>
If we continue to provide acute light pulses and plot their effects, working our way through every time-point in CT, we could create a phase response curve or PRC. The PRC below summarizes how the free-running mouse would respond to light at any CT. The PRC will be similar for others animals of the same species, and even different species have generally similar PRCs.
<div style="max-width:409px;height:auto;margin:auto;"><img src="http://ccb.ucsd.edu/_images/bioclock/EntrainmentSimulator/06_PRC.gif"></div>
<u>[[Proceed: A few things you should know about the PRC...|PRCExtra]]</u>
<span style="color:#223d8e;"> ''A Long FRP''</span>
Now, we will take a look at an organism with a long free-running period of around 24.5 h. Notice that this is the first time you have seen an actogram where the free-running onsets of activity "drift" to the right: the onset of activity is occurring 30 minutes ''later'' each day.
<img src="http://ccb.ucsd.edu/_images/bioclock/EntrainmentSimulator/10_LongFRP.gif" width="100%">
<span style="color:#223d8e;"><u>[[Got it, let's move on|LongEntrain]]</u>.</span>
<span style="color:#223d8e;">''Need a refresher?'' </span>
The Entrainment Simulator is built to help you play with and understand a few key concepts, but it's best if you have a basic, "textbook" understanding of these concepts before starting.
Take a look at each of the concepts below. If you've never heard of them, view the video for each concept to learn more. You can return to this page at any time by clicking "Review Basic Concepts" in the left navigation menu. (You can also use the ''⇦'' icon inside that menu if you ever want to go back to a previous passage. You can hide the whole menu by clicking the ''<'' icon at the top).
If you are already roughly familiar with these concepts, you're ready to <u>[[proceed to the Entrainment Simulator|LDactogram]].</u>
<div class="card-container"><div class="card"><iframe width="100%" height="auto" src="https://www.youtube.com/embed/1P4fPKC7238" frameborder="0" allow="accelerometer; autoplay; encrypted-media; gyroscope; picture-in-picture" allowfullscreen></iframe><div class="container"><p><b>FRP</b><br/><small>Length of an organism's "subjective" day/night cycle, without environmental cues.</small></p></div></div><div class="card"><iframe width="100%" height="auto" src="https://www.youtube.com/embed/jkdiis6o5dc" frameborder="0" allow="accelerometer; autoplay; encrypted-media; gyroscope; picture-in-picture" allowfullscreen></iframe><div class="container"><p><b>Actogram</b><br/><small>A graphical representation of an organism’s phases of activity and rest over the course of a day.</small></p></div></div><div class="card"><iframe width="100%" height="auto" src="https://www.youtube.com/embed/nHT5M8gZE20" frameborder="0" allow="accelerometer; autoplay; encrypted-media; gyroscope; picture-in-picture" allowfullscreen></iframe><div class="container"><p><b>CT & ZT</b><br/><small>Two different ways of discussing time: Circadian Time for free-running organisms, and Zeitgeber Time for organisms subjected to regular Zeitgebers.</small></p></div></div><div class="card"><iframe width="100%" height="auto" src="https://www.youtube.com/embed/gib7_ppLpXI" frameborder="0" allow="accelerometer; autoplay; encrypted-media; gyroscope; picture-in-picture" allowfullscreen></iframe><div class="container"><p><b>PRC</b><br/><small>A graph representing the varying effect an identical stimulus has on a circadian rhythm's phase, depending on the phase of circadian time at which it is applied.<br/>//also://<br/><b>Phase Shift</b><br/>A change (either an advance or a delay) in the phasing of an organism's free-running circadian rhythm, usually in response to an acute stimulus.</small></p></div></div></div>Let's look at some questions to facilitate your understanding!
<<set $Q1Array to [0,0,0]>><div class = "Q Ask"><span>Q1: Phase Shifts</span>
''Suppose that a mutant "ClockΔ19" mouse has a long free-running period: 𝛕=25 h. What kind of phase shift (e.g., on Day 6) is required to cause this mouse's onset of activity to occur after 24 hours (e.g., exactly 24 hours after the onset of activity occured on Day 5)?''
<ul><li>[[A. 1 hour delay|A1A][$Q1Array[0] to 1]]</li>
<li>[[B. 1 hour advance|A1B][$Q1Array[1] to 1]]</li>
<li>[[C. The ClockΔ19 mutant cannot be entrained|A1C][$Q1Array[2] to 1]]</li></ul>
</div>
<<if $Q1Array is undefined>><<set $Q1Array to [1,0,0]>><</if>>
<div class="Q Rev No"><span>Oops, not quite!</span>
Q1. Suppose that a mutant "ClockΔ19" mouse has a long free-running period: 𝛕=25 h. What kind of phase shift is required to entrain this mouse to a T=24 h cycle?<ul><li>''A. 1 hour delay''</li><li>B. 1 hour advance </li><li>C. The ClockΔ^^19^^ mutant cannot be entrained</li></ul></div>
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<<linkreplace "Want a hint?" t8n>>A phase ''delay'' would cause the mouse's activity to begin ''later'' each day. If you cause a 1 hour delay, it will be 26 hours before the next onset of activity...<</linkreplace>>
----
<div class = "Q Ask"><span>Let's try again.</span>
''Suppose that a mutant "ClockΔ19" mouse has a long free-running period: 𝛕=25 h. What kind of phase shift is required to entrain this mouse to a T=24 h cycle?''
<ul><<if $Q1Array[0] is 0>><li>[[A. 1 hour delay|A1A][$Q1Array[0] to 1]]</li><<else>><li>==A. 1 hour delay==</li><</if>>
<<if $Q1Array[1] is 0>><li>[[B. 1 hour advance|A1B][$Q1Array[1] to 1]]</li><<else>><li>==B. 1 hour advance==</li><</if>>
<<if $Q1Array[2] is 0>><li>[[C. The ClockΔ19 mutant cannot be entrained|A1C][$Q1Array[2] to 1]]</li><<else>><li>==C. The ClockΔ19 mutant cannot be entrained==</li><</if>>
</ul></div><div class="Q Rev Yes"><span>Good job!</span>
Q1. Suppose that a mutant "ClockΔ19" mouse has a long free-running period: 𝛕=25 h. What kind of phase shift is required to entrain this mouse to a T=24 h cycle?
<ul><li>A. 1 hour delay</li>
<li>''B. 1 hour advance ''</li>
<li>C. The ClockΔ^^19^^ mutant cannot be entrained</li></ul></div>
----
Right! A 1 h ''advance'' will cause the onset of activity to occur 1 h ''earlier'':
25 h - 1 h = 24 h.
<u>[[Proceed->Q2]]</u><div class="Q Ask"><span>Q2: Reading the PRC</span>
According to the PRC, at what circadian time should a light pulse be given to cause a phase advance of >2 hours?
<<set $Q2Array to [0,0,0,0]>>
<img src="http://ccb.ucsd.edu/_images/bioclock/EntrainmentSimulator/06_FullPrcNoPulses.png" border="0">
<ul><<if $Q2Array[0] is 0>><li>[[A. Early Subjective Night|A2A][$Q2Array[0] to 1]]</li><<else>><li>==A. Early Subjective Night==</li><</if>>
<<if $Q2Array[1] is 0>><li>[[B. Late Subjective Night|A2B][$Q2Array[1] to 1]]</li><<else>><li>==B. Late Subjective Night==</li><</if>>
<<if $Q2Array[2] is 0>><li>[[C. Early Subjective Day|A2C][$Q2Array[2] to 1]]</li><<else>><li>==C. Early Subjective Day==</li><</if>>
<<if $Q2Array[3] is 0>><li>[[D. Late Subjective Day|A2D][$Q2Array[3] to 1]]</li><<else>><li>==D. Late Subjective Day==</li><</if>></ul></div><<if $Q1Array is undefined>><<set $Q1Array to [0,0,1]>><</if>><div class="Q Rev No"><span>Whoa, that's a bold claim!</span>
Q1. Suppose that a mutant "ClockΔ19" mouse has a long free-running period: 𝛕=25 h. What kind of phase shift is required to entrain this mouse to a T=24 h cycle?
<ul><li>A. 1 hour delay</li>
<li>B. 1 hour advance </li>
<li>''C. The ClockΔ19 mutant cannot be entrained''</li></ul></div>
----
<<linkreplace "Want a hint?" t8n>>Take a look at a generic PRC:
<img src="http://ccb.ucsd.edu/_images/bioclock/EntrainmentSimulator/06_FullPrcNoPulses.png" border="0">
In order to entrain, we need to influence the onset of activity so that it occurs once every 24 h. Since the ClockΔ19 mutant has a free-running period of 𝛕=25 h, we just need a phase shift of one hour. As you can see from the PRC (particularly by looking at the Y-axis on the left side) this is very possible: we can easily produce both positive and negative phase shifts of >1 hour.<</linkreplace>>
----
<div class = "Q Ask"><span>Let's try again.</span>
''Suppose that a mutant "ClockΔ19" mouse has a long free-running period: 𝛕=25 h. What kind of phase shift is required to entrain this mouse to a T=24 h cycle?''
<ul><<if $Q1Array[0] is 0>><li>[[A. 1 hour delay|A1A][$Q1Array[0] to 1]]</li><<else>><li>==A. 1 hour delay==</li><</if>>
<<if $Q1Array[1] is 0>><li>[[B. 1 hour advance|A1B][$Q1Array[1] to 1]]</li><<else>><li>==B. 1 hour advance==</li><</if>>
<<if $Q1Array[2] is 0>><li>[[C. The ClockΔ19 mutant cannot be entrained|A1C][$Q1Array[2] to 1]]</li><<else>><li>==C. The ClockΔ19 mutant cannot be entrained==</li><</if>>
</ul></div> <<if $Q2Array is undefined>><<set $Q2Array to [1,0,0,0]>><</if>>
<div class="Q Rev No"><span>Oops, not quite!</span>
Q2. According to the PRC, at what circadian time should a light pulse be given to cause a phase advance of >2 hours?
<ul><li>''A. Early Subjective Night''</li>
<li>B. Late Subjective Night</li>
<li>C. Early Subjective Day</li>
<li>D. Late Subjective Day</li></ul></div>
----
<<linkreplace "Want a hint?" t8n>>Using the Y-axis (left side) of the PRC, find a point on the curve that produces the correct phase shift. Where does this point fall on the X-axis (bottom)? (Remember: a phase ''advance'' has a ''positive'' value on the Y-axis.)<</linkreplace>>
----
<div class="Q Ask"><span>''Let’s try again. ''</span>
''Q2. According to the PRC, at what circadian time should a light pulse be given to cause a phase advance of >2 hours?''
<img src="http://ccb.ucsd.edu/_images/bioclock/EntrainmentSimulator/06_FullPrcNoPulses.png" border="0">
<ul><<if $Q2Array[0] is 0>><li>[[A. Early Subjective Night|A2A][$Q2Array[0] to 1]]</li><<else>><li>==A. Early Subjective Night==</li><</if>>
<<if $Q2Array[1] is 0>><li>[[B. Late Subjective Night|A2B][$Q2Array[1] to 1]]</li><<else>><li>==B. Late Subjective Night==</li><</if>>
<<if $Q2Array[2] is 0>><li>[[C. Early Subjective Day|A2C][$Q2Array[2] to 1]]</li><<else>><li>==C. Early Subjective Day==</li><</if>>
<<if $Q2Array[3] is 0>><li>[[D. Late Subjective Day|A2D][$Q2Array[3] to 1]]</li><<else>><li>==D. Late Subjective Day==</li><</if>></ul></div><<if $Q2Array is undefined>><<set $Q2Array to [0,1,0,0]>><</if>><div class="Q Rev Yes"><span>Good Job!</span>
Q2. According to the PRC, at what circadian time should a light pulse be given to cause a phase advance of >2 hours?
<ul><li>A. Early Subjective Night</li>
<li>''B. Late Subjective Night''</li>
<li>C. Early Subjective Day</li>
<li>D. Late Subjective Day</li></ul></div>
----
Right! Giving a light pulse in late subjective night could cause a >2 hour advance.
<img src="http://ccb.ucsd.edu/_images/bioclock/EntrainmentSimulator/06_Q2AC.jpg">
<u>[[Proceed->RptPulses]]</u><<if $Q2Array is undefined>><<set $Q2Array to [0,0,1,0]>><</if>>
<div class="Q Rev No"><span>Oops, not quite!</span>
Q2. According to the PRC, at what circadian time should a light pulse be given to cause a 2 hour advance?
<ul><li>A. Early Subjective Night</li>
<li>B. Late Subjective Night</li>
<li>__''C. Early Subjective Day''__</li>
<li>D. Late Subjective Day</li></ul></div>
----
<<linkreplace "Want a hint?" t8n>>Using the Y-axis (left side) of the PRC, find a point on the curve that produces the correct phase shift. Where does this point fall on the X-axis (bottom)? <</linkreplace>>
----
<div class="Q Ask"><span>''Let’s try again. ''</span>
''Q2. According to the PRC, at what circadian time should a light pulse be given to cause a phase advance of >2 hours?''
<img src="http://ccb.ucsd.edu/_images/bioclock/EntrainmentSimulator/06_FullPrcNoPulses.png" border="0">
<ul><<if $Q2Array[0] is 0>><li>[[A. Early Subjective Night|A2A][$Q2Array[0] to 1]]</li><<else>><li>==A. Early Subjective Night==</li><</if>>
<<if $Q2Array[1] is 0>><li>[[B. Late Subjective Night|A2B][$Q2Array[1] to 1]]</li><<else>><li>==B. Late Subjective Night==</li><</if>>
<<if $Q2Array[2] is 0>><li>[[C. Early Subjective Day|A2C][$Q2Array[2] to 1]]</li><<else>><li>==C. Early Subjective Day==</li><</if>>
<<if $Q2Array[3] is 0>><li>[[D. Late Subjective Day|A2D][$Q2Array[3] to 1]]</li><<else>><li>==D. Late Subjective Day==</li><</if>></ul></div><<if $Q2Array is undefined>><<set $Q2Array to [0,0,0,1]>><</if>>
<div class="Q Rev No"><span>Oops, not quite!</span>
Q2. According to the PRC, at what circadian time should a light pulse be given to cause a phase advance of >2 hours?
<ul><li>A. Early Subjective Night</li>
<li>B. Late Subjective Night</li>
<li>C. Early Subjective Day</li>
<li>''D. Late Subjective Day''</li></ul></div>
----
<<linkreplace "Want a hint?" t8n>>Using the Y-axis (left side) of the PRC, find a point on the curve that produces the correct phase shift. Where does this point fall on the X-axis (bottom)?<</linkreplace>>
----
<div class="Q Ask"><span>''Let’s try again. ''</span>
''Q2. According to the PRC, at what circadian time should a light pulse be given to cause a phase advance of >2 hours?''
<img src="http://ccb.ucsd.edu/_images/bioclock/EntrainmentSimulator/06_FullPrcNoPulses.png" border="0">
<ul><<if $Q2Array[0] is 0>><li>[[A. Early Subjective Night|A2A][$Q2Array[0] to 1]]</li><<else>><li>==A. Early Subjective Night==</li><</if>>
<<if $Q2Array[1] is 0>><li>[[B. Late Subjective Night|A2B][$Q2Array[1] to 1]]</li><<else>><li>==B. Late Subjective Night==</li><</if>>
<<if $Q2Array[2] is 0>><li>[[C. Early Subjective Day|A2C][$Q2Array[2] to 1]]</li><<else>><li>==C. Early Subjective Day==</li><</if>>
<<if $Q2Array[3] is 0>><li>[[D. Late Subjective Day|A2D][$Q2Array[3] to 1]]</li><<else>><li>==D. Late Subjective Day==</li><</if>></ul></div><span style="color:#f48642;">Congratulations!</span>
You have successfully completed the entrainment simulator.
<img id="end" src="http://ccb.ucsd.edu/_images/bioclock/EntrainmentSimulator/11_End.png" border="0">
<u>[[Return to Welcome Screen->START]]</u> | <u>[[Watch Our Documentary|https://www.youtube.com/channel/UCtoACN4wH06iJLRRXo0i_ig]]</u> | <u>[[Visit Our Website|https://ccb.ucsd.edu/the-bioclock-studio/index.html]]</u>
<p class="authors" >//Created 2019, by://</p><p class="authors" style="padding-left:42px;text-indent:-22px;"><span style="color:#223d8e;">//Jiawei Liu, Alisa Kim, Allen Gee, David Welkie, Karen Tonsfeldt, Ben Sheredos, Michael Gorman, and Susan Golden//</span></p><p class="authors" >//Extended 2020, by://</p><p class="authors" style="padding-left:42px;text-indent:-22px;"><span style="color:#223d8e;">//Dan Ly, Lukas Lee, Saisantosh Attaluri, Elizabeth Harrison, Ben Sheredos, Michael Gorman, and Susan Golden//</span></p><html><head><meta name="viewport" content="width=device-width, initial-scale=1"><style> #end:hover {animation: shake 0.5s;animation-iteration-count: infinite;} @keyframes shake {
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<<button "Building a PRC" "MPulses">><</button>><<button "Exploring Acute Pulses" "ActoSliderBar">><</button>><<button "Review Qs about Pulses" Q1>><</button>><<button "Exploring Entrainment" RptPulses>><</button>><<button "Entrainment with a Short FRP" ShortPeriod>><</button>><<button "Entrainment with a Long FRP" LongPeriod>><</button>><<button "The Limits of Entrainment" Limits>><</button>><<button "Skeleton Photoperiod" SkeletonPhotoperiod>><</button>>
//(If this is empty, then nothing is currently being tested.)//
----
<span style="color:#223d8e;"> ''Circadian Time (CT)'' </span>
A normal mouse's free-running period is 23.5 h: this is the length of time that the mouse's circadian clock "thinks" is one day, in the absence of external cues. Just as we divide a normal day into 24 hours, we will divide the mouse's whole 23.5 h subjective day/night cycle into 24 "circadian hours." By convention, the onset of activity (left edge of dark bar) is used to fix the time-point of CT 12, or the beginning of subjective night, in nocturnal organisms like our mouse. (In diurnal organisms, the onset of activity would be used to fix CT 0/24, the start of subjective day.)
<img src="http://ccb.ucsd.edu/_images/bioclock/EntrainmentSimulator/02_CT.jpg">
Circadian time is always linked to the organism's rhythm, not to environmental time as would be reflected by a clock on the wall or on your phone.
<u>[[Proceed: Play with some light pulses->MPulses]]</u><span style="color:#223d8e;"> ''Details about the PRC''</span>
There are two special regions of the PRC worth noting. One of them is the interval near the middle of subjective day (marked with the blue circle below). We'll discuss the other one a little later on.
<div style="max-width:409px;height:auto;margin:auto;"><img src="http://ccb.ucsd.edu/_images/bioclock/EntrainmentSimulator/06_PrcExtra.jpg"></div>
<p style="line-height:1.1em;margin:auto 2em auto 2em;"><span style="color:blue;">''The Dead Zone:''</span>
Light pulses applied in the middle of subjective day are ineffective in producing any phase shifts. (Intuitively: the circadian clock is already predicting that there will probably be light in the middle of subjective day, so a light pulse at that time shouldn't cause the clock to make any adjustments.)</p>
''In other words:'' if you want to cause an organism's onset of activity to deviate from the FRP using light, you'll need to avoid providing pulses in this region of the PRC.
Got it. Now <u>[[let's really explore the effects of light pulses!!|ActoSliderBar]]</u>
<span style="color:#223d8e;"> ''Entrainment II: Repeated Pulses at ZT 6'' </span>
At the bottom of this page you can explore in detail what happens when we repeatedly apply a light pulse at ZT 6. As you do so, enter information to answer the following questions: when you've answered all the questions correctly, you can move on.<<set $obs to "empty">><<set $Correct1 to "11">><<set $Correct1t to "ELEVEN">><<set $Correct2 to "1">><<set $Correct3 to "2">><<set $Correct3t to "TWO">>
<div style="border:1px solid #000; border-radius:5px;"><div style="margin:auto;"><span style="font-size:small;"> To submit text answers, hit the Enter key or click outside the input boxes below.</span>
|<p class="ZTQuiz"><span class ="unknown" id="Q1">Q1:</span> How many days of light pulses does it take for the mouse to entrain? <<linkreplace "(Need help?)" t8n>>(Remember, the first 5 days don't involve pulses. <<linkreplace "Need more help?" t8n>>Go through the slides to find the day on which entrainment occurs, then subtract 5.<</linkreplace>>)<</linkreplace>></p>|<div class="badge qmark" id="Badge1"></div>|<<textbox "$Days" "">><span style="font-size:small;"> (Enter # only)</span>|
|<p class="ZTQuiz"><span class ="unknown" id="Q2">Q2:</span> On the path to entrainment, which of the following phase shifts did you observe? <<linkreplace "(Need help?)" t8n>>(Remember, free-running is ''not'' a phase shift: only reactions caused by a Zeitgeber like a pulse of light count as phase shifts. <<linkreplace "Need more help?" t8n>> Pay attention to the PRCs below each slide: advances are positive values on the y-axis and delays are negative values.<</linkreplace>>)<</linkreplace>></p>|<div class="badge qmark" id="Badge2"></div>|<ul class="Qlist"><li><label><<radiobutton "$obs" "0">>Phase Advances only</label></li><li><label><<radiobutton "$obs" "1">>Phase Delays only</label></li><li><label><<radiobutton "$obs" "2">>Both Advances and Delays</label></li><li><label><<radiobutton "$obs" "3">>Neither</label></li></ul>|
|<p class="ZTQuiz"><span class="unknown" id="Q3">Q3:</span> After entrainment, what is the phase angle (expressed as: how many hours after the light pulse does activity begin)?</p>|<div class="badge qmark" id="Badge3"></div>|<<textbox "$Psi" "">><span style="font-size:small;"> (Enter # only)</span>||
<div class="gate closed"><span id="gate">==PROCEED==</span></div></div></div>
<p>Click through the images below (using the dots at the top) for an explanation.</p><p style="font-size:smaller;line-height:1.1em;margin-left:20px;">''NOTE:'' the X-axis of the actogram is where ZT is indicated. Values for CT are always determined independently of ZT, by comparing the phase of the pulse to the onset of activity (here, CT 12).</p>
<div style="width:100%;"><ul class="slides" style="display:block;"><input type="radio" name="radio-btn" id="img-1" checked /><li class="slide-container"><div class="slide"><img src="http://ccb.ucsd.edu/_images/bioclock/EntrainmentSimulator/09_ZT6_02.JPG"><p>''Days 1-5:'' The mouse free-runs as usual with its short FRP. On the left, you can see the end-points of the mouse's activity for the past 5 days. Starting on Day 6, we plan to apply a pulse of light every day at ZT 6. Let's see how this affects the mouse's activity.</p></div></li><input type="radio" name="radio-btn" id="img-2" /><li class="slide-container"><div class="slide"><img src="http://ccb.ucsd.edu/_images/bioclock/EntrainmentSimulator/09_ZT6_03.JPG"><p><img src="http://ccb.ucsd.edu/_images/bioclock/EntrainmentSimulator/08_CaptionPRC06.png" style="max-width:150px;float:right;z-index:9; padding-left:10px;padding-right:1em;padding-bottom:2em;">''Days 6-11: '' On Day 6, the light pulse lands at around CT 6, and thus has no effect. There is likewise no effect as the mouse free-runs for another 5 days: the pulse continues to land in the Dead Zone. ''Note:'' our pulse is constant at ZT 6, but it is falling at progressively later CT each day as the mouse continues to free-run. Each day, we need to determine the new phase of CT at which our fixed ZT pulse is falling. </p></div></li><input type="radio" name="radio-btn" id="img-3" /><li class="slide-container"><div class="slide"><img src="http://ccb.ucsd.edu/_images/bioclock/EntrainmentSimulator/09_ZT6_04.JPG" /><p><img src="http://ccb.ucsd.edu/_images/bioclock/EntrainmentSimulator/08_CaptionPRC09.png" style="max-width:150px;float:right;z-index:9; padding-left:10px;padding-right:1em;padding-bottom:2em;">''Day 12:'' The light pulse now lands at CT 9. As indicated on the PRC, this causes a small phase delay of .25 h, which is not sufficient to fully counteract the mouse's short FRP of 23.5 h. The result is that the onset of activity on Day 12 occurs .25 h earlier than it did on Day 11. (The dotted line on the left graphic shows where the onset of activity would have occurred if the mouse were still free-running).</p></div></li><input type="radio" name="radio-btn" id="img-4" /><li class="slide-container"><div class="slide"><img src="http://ccb.ucsd.edu/_images/bioclock/EntrainmentSimulator/09_ZT6_05.JPG" /><p><img src="http://ccb.ucsd.edu/_images/bioclock/EntrainmentSimulator/08_CaptionPRC09.png" style="max-width:150px;float:right;z-index:9; padding-left:10px;padding-right:1em;padding-bottom:2em;">''Day 13:'' The pulse now lands at about CT 9.25. This produces a small phase delay of ~0.3 h -- which partially counteracts the short FRP so that the onset of activity on Day 13 occurs ~0.2 h later than it did on Day 12.</p></div></li><input type="radio" name="radio-btn" id="img-5" /><li class="slide-container"><div class="slide"><img src="http://ccb.ucsd.edu/_images/bioclock/EntrainmentSimulator/09_ZT6_06.JPG" /><p><img src="http://ccb.ucsd.edu/_images/bioclock/EntrainmentSimulator/08_CaptionPRC09.png" style="max-width:150px;float:right;z-index:9; padding-left:10px;padding-right:1em;padding-bottom:2em;">''Day 14:'' The pulse now lands at about CT ~9.45. This produces a small phase delay of ~0.37 h -- which partially counteracts the short FRP so that the onset of activity on Day 14 occurs ~0.13 h later than it did on Day 13.</p></div></li><input type="radio" name="radio-btn" id="img-6" /><li class="slide-container"><div class="slide"><img src="http://ccb.ucsd.edu/_images/bioclock/EntrainmentSimulator/09_ZT6_07.JPG" /><p><img src="http://ccb.ucsd.edu/_images/bioclock/EntrainmentSimulator/08_CaptionPRC10.png" style="max-width:150px;float:right;z-index:9; padding-left:10px;padding-right:1em;padding-bottom:2em;">''Day 15:'' The pulse now lands at about CT ~9.58. This produces a small phase delay of ~0.42 h -- which almost fully counteracts the short FRP so that the onset of activity on Day 15 occurs only ~0.08 h later than it did on Day 14.</p></div></li><input type="radio" name="radio-btn" id="img-7" /><li class="slide-container"><div class="slide"><img src="http://ccb.ucsd.edu/_images/bioclock/EntrainmentSimulator/09_ZT6_08.JPG" /><p><img src="http://ccb.ucsd.edu/_images/bioclock/EntrainmentSimulator/08_CaptionPRC10.png" style="max-width:150px;float:right;z-index:9; padding-left:10px;padding-right:1em;padding-bottom:2em;">''Day 16:'' You get the idea: the pulse is landing increasingly closer to CT 10. When it does land at CT 10, this produces a phase delay of 0.5 h -- which exactly counteracts the short FRP so that the onset of activity on Day 16 occurs at exactly the same ZT that it occurred on Day 15. The mouse is now entrained: the pulse will always land at CT 10, will always produce a delay of 0.5 h, and will always counteract the FRP so that the onset activity occurs with an interval of 24 h.</p></div></li><input type="radio" name="radio-btn" id="img-8" /><li class="slide-container"><div class="slide"><img src="http://ccb.ucsd.edu/_images/bioclock/EntrainmentSimulator/09_ZT6_09.jpg" /><p>''Phase Angle (Psi):'' The mouse entrains with repeated pulses so long as they land at CT 10. The entraining pulse occurs ~2 h before the onset of activity. We call the difference between these two values the "phase angle of entrainment," symbolized by the Greek letter psi (ψ). For this mouse, the phase angle of entrainment to a 24 h period is about 2 h.</p></div></li><li class="nav-dots"><label for="img-1" class="nav-dot" id="img-dot-1"></label><label for="img-2" class="nav-dot" id="img-dot-2"></label><label for="img-3" class="nav-dot" id="img-dot-3"></label><label for="img-4" class="nav-dot" id="img-dot-4"></label><label for="img-5" class="nav-dot" id="img-dot-5"></label><label for="img-6" class="nav-dot" id="img-dot-6"></label><label for="img-7" class="nav-dot" id="img-dot-7"></label><label for="img-8" class="nav-dot" id="img-dot-8"></label></li></ul></div>
<<silently>><<repeat 1s>><<if setup.trim($Days) is $Correct1 || setup.trim(setup.GoBig($Days)) is $Correct1t>><<addclass "#Badge1" "check">><<removeclass "#Badge1" "qmark">><<removeclass "#Badge1" "ex">><<addclass "#Q1" "correct">><<removeclass "#Q1" "unknown">><<removeclass "#Q1" "wrong">><<elseif setup.trim($Days) isnot "" && setup.trim($Days) isnot "">><<addclass "#Badge1" "ex">><<removeclass "#Badge1" "qmark">><<removeclass "#Badge1" "check">><<addclass "#Q1" "wrong">><<removeclass "#Q1" "unknown">><<removeclass "#Q1" "correct">><<elseif setup.trim($Days) is "" || setup.trim($Days) is "">><<addclass "#Badge1" "qmark">><<removeclass "#Badge1" "check">><<removeclass "#Badge1" "ex">><<addclass "#Q1" "unknown">><<removeclass "#Q1" "correct">><<removeclass "#Q1" "wrong">><</if>><<if $obs is $Correct2>><<addclass "#Badge2" "check">><<removeclass "#Badge2" "qmark">><<removeclass "#Badge2" "ex">><<addclass "#Q2" "correct">><<removeclass "#Badge2" "unknown">><<elseif $obs isnot "empty">><<addclass "#Badge2" "ex">><<removeclass "#Badge2" "qmark">><<removeclass "#Badge2" "check">><<addclass "#Q2" "wrong">><<removeclass "#Q2" "unknown">><<removeclass "#Q2" "correct">><</if>><<if setup.trim($Psi) is $Correct3 || setup.trim(setup.GoBig($Psi)) is $Correct3t>><<addclass "#Badge3" "check">><<removeclass "#Badge3" "qmark">><<removeclass "#Badge3" "ex">><<addclass "#Q3" "correct">><<removeclass "#Q3" "unknown">><<removeclass "#Q3" "wrong">><<elseif setup.trim($Psi) isnot "" && setup.trim($Psi) isnot "">><<addclass "#Badge3" "ex">><<removeclass "#Badge3" "qmark">><<removeclass "#Badge3" "check">><<addclass "#Q3" "wrong">><<removeclass "#Q3" "unknown">><<removeclass "#Q3" "correct">><<elseif setup.trim($Psi) is "" || setup.trim($Psi) is "">><<addclass "#Badge3" "qmark">><<removeclass "#Badge3" "check">><<removeclass "#Badge3" "ex">><<addclass "#Q3" "unknown">><<removeclass "#Q3" "correct">><<removeclass "#Q3" "wrong">><</if>><<if (setup.trim($Days) is $Correct1 || setup.trim(setup.GoBig($Days)) is $Correct1t) && $obs is $Correct2 && (setup.trim($Psi) is $Correct3 || setup.trim(setup.GoBig($Psi)) is $Correct3t)>><<addclass ".gate" "open">><<removeclass ".gate" "closed">><<replace "#gate">><u>[[Proceed|ZT14]]</u><</replace>><<elseif setup.trim($Days) isnot $Correct1 || setup.trim($Days) isnot $Correct1t ||$obs isnot $Correct2 || setup.trim($Psi) isnot $Correct3 || setup.trim($Psi) isnot $Correct3t>><<addclass ".gate" "closed">><<removeclass ".gate" "open">><<replace "#gate">>==Proceed==<</replace>><</if>><</repeat>><</silently>><span style="color:#223d8e;"> ''Entrainment III: Repeated Pulses at ZT 14'' </span>
At the bottom of this page you can explore in detail what happens when we repeatedly apply a light pulse at ZT 14. As you do so, enter information to answer the following questions: when you've answered all the questions correctly, you can move on.<<set $obs to "empty">><<set $Correct1 to "5">><<set $Correct1t to "FIVE">><<set $Correct2 to "1">><<set $Correct3 to "2">><<set $Correct3t to "TWO">>
<div style="border:1px solid #000; border-radius:5px;"><div style="margin:auto;"><span style="font-size:small;"> To submit text answers, hit the Enter key or click outside the input boxes below.</span>
|<p class="ZTQuiz"><span class ="unknown" id="Q1">Q1:</span> How many days of light pulses does it take for the mouse to entrain? <<linkreplace "(Need help?)" t8n>>(Remember, the first 5 days don't involve pulses. <<linkreplace "Need more help?" t8n>>Go through the slides to find the day on which entrainment occurs, then subtract 5.<</linkreplace>>)<</linkreplace>></p>|<div class="badge qmark" id="Badge1"></div>|<<textbox "$Days" "">><span style="font-size:small;"> (Enter # only)</span>||
|<p class="ZTQuiz"><span class ="unknown" id="Q2">Q2:</span> On the path to entrainment, which of the following phase shifts did you observe? <<linkreplace "(Need help?)" t8n>>(Remember, free-running is ''not'' a phase shift: only reactions caused by a Zeitgeber like a pulse of light count as phase shifts. <<linkreplace "Need more help?" t8n>> Pay attention to the PRCs below each slide: advances are positive values on the y-axis and delays are negative values.<</linkreplace>>)<</linkreplace>></p>|<div class="badge qmark" id="Badge2"></div>|<ul class="Qlist"><li><label><<radiobutton "$obs" "0">>Phase Advances only</label></li><li><label><<radiobutton "$obs" "1">>Phase Delays only</label></li><li><label><<radiobutton "$obs" "2">>Both Advances and Delays</label></li><li><label><<radiobutton "$obs" "3">>Neither</label></li></ul>|
|<p class="ZTQuiz"><span class="unknown" id="Q3">Q3:</span> After entrainment, what is the phase angle (expressed as: how many hours after the light pulse does activity begin)?</p>|<div class="badge qmark" id="Badge3"></div>|<<textbox "$Psi" "">><span style="font-size:small;"> (Enter # only)</span>||
<div class="gate closed"><span id="gate">==PROCEED==</span></div></div></div>
<p>Click through the images below (using the dots at the top) for an explanation.</p><p style="font-size:smaller;line-height:1.1em;margin-left:20px;">''NOTE:'' the X-axis of the actogram is where ZT is indicated. Values for CT are always determined independently of ZT, by comparing the phase of the pulse to the onset of activity (here, CT 12).</p>
<div style="width:100%;"><ul class="slides" style="display:block;"><input type="radio" name="radio-btn" id="img-1" checked /><li class="slide-container"><div class="slide"><img src="http://ccb.ucsd.edu/_images/bioclock/EntrainmentSimulator/09_ZT14_02.JPG"><p>''Days 1-5:'' The mouse free-runs as usual with its short FRP. Starting on Day 6, we plan to apply a pulse of light every day at ZT 14. Let's see how this affects the mouse's activity.</p></div></li><input type="radio" name="radio-btn" id="img-2" /><li class="slide-container"><div class="slide"><img src="http://ccb.ucsd.edu/_images/bioclock/EntrainmentSimulator/09_ZT14_03.JPG"><p><img src="http://ccb.ucsd.edu/_images/bioclock/EntrainmentSimulator/08_CaptionPRC14.png" style="max-width:150px;float:right;z-index:9; padding-left:10px;padding-right:1em;padding-bottom:2em;">''Day 6:'' The light pulse lands at around CT 14.5. As indicated on the PRC, this produces a large phase delay of ~3.5 h. Since the pulse occurs after the onset of activity, its effect is initially seen by the delayed offset of activity on Day 6. (The dotted line in the left graphic shows when the offset of activity would normally have occurred on Day 6.)</p></div></li><input type="radio" name="radio-btn" id="img-3" /><li class="slide-container"><div class="slide"><img src="http://ccb.ucsd.edu/_images/bioclock/EntrainmentSimulator/09_ZT14_04.JPG"><p><img src="http://ccb.ucsd.edu/_images/bioclock/EntrainmentSimulator/08_CaptionPRC11.png" style="max-width:150px;float:right;z-index:9; padding-left:10px;padding-right:1em;padding-bottom:2em;">''Day 7:'' The light pulse now lands at about CT 11.5. As indicated on the PRC, this causes a moderate phase delay of about 1.25 h. This more than counteracts the mouse's short FRP, and the result is that the onset of activity on Day 7 occurs .75 h later than it would have. Note: The dotted line on the left graphic shows where the onset of activity would have occurred if the mouse had not received the 2 pulses on Days 6 and 7 - both of these pulses have delayed the onset of activity on Day 7.</p></div></li><input type="radio" name="radio-btn" id="img-4" /><li class="slide-container"><div class="slide"><img src="http://ccb.ucsd.edu/_images/bioclock/EntrainmentSimulator/09_ZT14_05.JPG"><p><img src="http://ccb.ucsd.edu/_images/bioclock/EntrainmentSimulator/08_CaptionPRC11.png" style="max-width:150px;float:right;z-index:9; padding-left:10px;padding-right:1em;padding-bottom:2em;">''Day 8:'' The pulse now lands at about CT 10.75. This produces a phase delay of ~0.7 h. This more than counteracts the short FRP so that the onset of activity on Day 8 occurs ~0.2 h later than it did on Day 7.</p></div></li><input type="radio" name="radio-btn" id="img-5" /><li class="slide-container"><div class="slide"><img src="http://ccb.ucsd.edu/_images/bioclock/EntrainmentSimulator/09_ZT14_06.JPG"><p><img src="http://ccb.ucsd.edu/_images/bioclock/EntrainmentSimulator/08_CaptionPRC10.png" style="max-width:150px;float:right;z-index:9; padding-left:10px;padding-right:1em;padding-bottom:2em;">''Day 9:'' The pulse now lands at about CT 10.55. As suggested by the PRC, this produces a phase delay of ~0.6 h. This more than counteracts the short FRP so that the onset of activity on Day 9 occurs ~0.1 h later than it did on Day 8.</p></div></li><input type="radio" name="radio-btn" id="img-6" /><li class="slide-container"><div class="slide"><img src="http://ccb.ucsd.edu/_images/bioclock/EntrainmentSimulator/09_ZT14_07.JPG"><p><img src="http://ccb.ucsd.edu/_images/bioclock/EntrainmentSimulator/08_CaptionPRC10.png" style="max-width:150px;float:right;z-index:9; padding-left:10px;padding-right:1em;padding-bottom:2em;">''Day 10:'' You get the idea: the pulse is landing increasingly closer to CT 10. When the pulse lands at CT 10, this will produce a phase delay of 0.5 h -- which exactly counteracts the short FRP so that the onset of activity on Day 10 occurs at exactly the same ZT that it occurred on Day 9. The mouse is now entrained: the pulse will always land at CT 10, will always produce a delay of 0.5 h, and will always counteract the FRP so that the onset activity occurs with an interval of 24 h.</p></div></li><input type="radio" name="radio-btn" id="img-7" /><li class="slide-container"><div class="slide"><img src="http://ccb.ucsd.edu/_images/bioclock/EntrainmentSimulator/09_ZT14_08.jpg" /><p>''Phase Angle (Psi):'' The mouse entrains with repeated pulses so long as they land at CT 10. The entraining pulse occurs ~2 h before the onset of activity. We call the difference between these two values the "phase angle of entrainment," symbolized by the Greek letter psi (ψ). For this mouse, the phase angle of entrainment to a 24 h period is about 2 h.</p></div></li>
<li class="nav-dots"><label for="img-1" class="nav-dot" id="img-dot-1"></label><label for="img-2" class="nav-dot" id="img-dot-2"></label><label for="img-3" class="nav-dot" id="img-dot-3"></label><label for="img-4" class="nav-dot" id="img-dot-4"></label><label for="img-5" class="nav-dot" id="img-dot-5"></label><label for="img-6" class="nav-dot" id="img-dot-6"></label><label for="img-7" class="nav-dot" id="img-dot-7"></label></li></ul></div>
<<silently>><<repeat 1s>><<if setup.trim($Days) is $Correct1 || setup.trim(setup.GoBig($Days)) is $Correct1t>><<addclass "#Badge1" "check">><<removeclass "#Badge1" "qmark">><<removeclass "#Badge1" "ex">><<addclass "#Q1" "correct">><<removeclass "#Q1" "unknown">><<removeclass "#Q1" "wrong">><<elseif setup.trim($Days) isnot "" && setup.trim($Days) isnot "">><<addclass "#Badge1" "ex">><<removeclass "#Badge1" "qmark">><<removeclass "#Badge1" "check">><<addclass "#Q1" "wrong">><<removeclass "#Q1" "unknown">><<removeclass "#Q1" "correct">><<elseif setup.trim($Days) is "" || setup.trim($Days) is "">><<addclass "#Badge1" "qmark">><<removeclass "#Badge1" "check">><<removeclass "#Badge1" "ex">><<addclass "#Q1" "unknown">><<removeclass "#Q1" "correct">><<removeclass "#Q1" "wrong">><</if>><<if $obs is $Correct2>><<addclass "#Badge2" "check">><<removeclass "#Badge2" "qmark">><<removeclass "#Badge2" "ex">><<addclass "#Q2" "correct">><<removeclass "#Badge2" "unknown">><<elseif $obs isnot "empty">><<addclass "#Badge2" "ex">><<removeclass "#Badge2" "qmark">><<removeclass "#Badge2" "check">><<addclass "#Q2" "wrong">><<removeclass "#Q2" "unknown">><<removeclass "#Q2" "correct">><</if>><<if setup.trim($Psi) is $Correct3 || setup.trim(setup.GoBig($Psi)) is $Correct3t>><<addclass "#Badge3" "check">><<removeclass "#Badge3" "qmark">><<removeclass "#Badge3" "ex">><<addclass "#Q3" "correct">><<removeclass "#Q3" "unknown">><<removeclass "#Q3" "wrong">><<elseif setup.trim($Psi) isnot "" && setup.trim($Psi) isnot "">><<addclass "#Badge3" "ex">><<removeclass "#Badge3" "qmark">><<removeclass "#Badge3" "check">><<addclass "#Q3" "wrong">><<removeclass "#Q3" "unknown">><<removeclass "#Q3" "correct">><<elseif setup.trim($Psi) is "" || setup.trim($Psi) is "">><<addclass "#Badge3" "qmark">><<removeclass "#Badge3" "check">><<removeclass "#Badge3" "ex">><<addclass "#Q3" "unknown">><<removeclass "#Q3" "correct">><<removeclass "#Q3" "wrong">><</if>>
<<if (setup.trim($Days) is $Correct1 || setup.trim(setup.GoBig($Days)) is $Correct1t) && $obs is $Correct2 && (setup.trim($Psi) is $Correct3 || setup.trim(setup.GoBig($Psi)) is $Correct3t)>><<addclass ".gate" "open">><<removeclass ".gate" "closed">><<replace "#gate">><u>[[Proceed|ZT22]]</u><</replace>><<elseif setup.trim($Days) isnot $Correct1 || setup.trim($Days) isnot $Correct1t ||$obs isnot $Correct2 || setup.trim($Psi) isnot $Correct3 || setup.trim($Psi) isnot $Correct3t>><<addclass ".gate" "closed">><<removeclass ".gate" "open">><<replace "#gate">>==Proceed==<</replace>><</if>><</repeat>><</silently>><span style="color:#223d8e;"> ''Entrainment IV: Repeated Pulses at ZT 22'' </span>
At the bottom of this page you can explore in detail what happens when we repeatedly apply a light pulse at ZT 22. As you do so, enter information to answer the following questions: when you've answered all the questions correctly, you can move on.<<set $obs to "empty">><<set $Correct1 to "19">><<set $Correct1t to "NINETEEN">><<set $Correct2 to "2">><<set $Correct3 to "2">><<set $Correct3t to "TWO">>
<div style="border:1px solid #000; border-radius:5px;"><div style="margin:auto;"><span style="font-size:small;"> To submit text answers, hit the Enter key or click outside the input boxes below.</span>
|<p class="ZTQuiz"><span class ="unknown" id="Q1">Q1:</span> How many days of light pulses does it take for the mouse to entrain? <<linkreplace "(Need help?)" t8n>>(Remember, the first 5 days don't involve pulses. <<linkreplace "Need more help?" t8n>>Go through the slides to find the day on which entrainment occurs, then subtract 5.<</linkreplace>>)<</linkreplace>></p>|<div class="badge qmark" id="Badge1"></div>|<<textbox "$Days" "">><span style="font-size:small;"> (Enter # only)</span>||
|<p class="ZTQuiz"><span class ="unknown" id="Q2">Q2:</span> On the path to entrainment, which of the following phase shifts did you observe? <<linkreplace "(Need help?)" t8n>>(Remember, free-running is ''not'' a phase shift: only reactions caused by a Zeitgeber like a pulse of light count as phase shifts. <<linkreplace "Need more help?" t8n>> Pay attention to the PRCs below each slide: advances are positive values on the y-axis and delays are negative values.<</linkreplace>>)<</linkreplace>></p>|<div class="badge qmark" id="Badge2"></div>|<ul class="Qlist"><li><label><<radiobutton "$obs" "0">>Phase Advances only</label></li><li><label><<radiobutton "$obs" "1">>Phase Delays only</label></li><li><label><<radiobutton "$obs" "2">>Both Advances and Delays</label></li><li><label><<radiobutton "$obs" "3">>Neither</label></li></ul>|
|<p class="ZTQuiz"><span class="unknown" id="Q3">Q3:</span> After entrainment, what is the phase angle (expressed as: how many hours after the light pulse does activity begin)?</p>|<div class="badge qmark" id="Badge3"></div>|<<textbox "$Psi" "">><span style="font-size:small;"> (Enter # only)</span>||
<div class="gate closed"><span id="gate">==PROCEED==</span></div></div></div>
<p>Click through the images below (using the dots at the top) for an explanation.</p><p style="font-size:smaller;line-height:1.1em;margin-left:20px;">''NOTE:'' the X-axis of the actogram is where ZT is indicated. Values for CT are always determined independently of ZT, by comparing the phase of the pulse to the onset of activity (here, CT 12).</p>
<div style="width:100%;"><ul class="slides" style="display:block;"><input type="radio" name="radio-btn" id="img-1" checked /><li class="slide-container"><div class="slide"><img src="http://ccb.ucsd.edu/_images/bioclock/EntrainmentSimulator/09_ZT22_02.JPG"><p>''Days 1-5:'' The mouse free-runs as usual with its short FRP. Starting on Day 6, we plan to apply a pulse of light every day at ZT 22. Let's see how this affects the mouse's activity.</p></div></li><input type="radio" name="radio-btn" id="img-2" /><li class="slide-container"><div class="slide"><img src="http://ccb.ucsd.edu/_images/bioclock/EntrainmentSimulator/09_ZT22_03.JPG"><p><img src="http://ccb.ucsd.edu/_images/bioclock/EntrainmentSimulator/08_CaptionPRC22.png" style="max-width:150px;float:right;z-index:9; padding-left:10px;padding-right:1em;padding-bottom:2em;">''Day 6:'' The light pulse lands at around CT 22. As indicated on the PRC, this causes a phase advance of about 2 h. Since the pulse occurs after the onset of activity, its effect is initially seen by the advanced offset of activity on Day 6. However, the advance caused by the pulse will also supplement the mouse's FRP causing the onset of activity on Day 7 to occur 2.5 h earlier than it did on Day 6.</p></div></li><input type="radio" name="radio-btn" id="img-3" /><li class="slide-container"><div class="slide"><img src="http://ccb.ucsd.edu/_images/bioclock/EntrainmentSimulator/09_ZT22_04.JPG"><p><img src="http://ccb.ucsd.edu/_images/bioclock/EntrainmentSimulator/08_CaptionPRC24.png" style="max-width:150px;float:right;z-index:9; padding-left:10px;padding-right:1em;padding-bottom:2em;">''Day 7:'' The light pulse now lands at about CT 24. As indicated on the PRC, this causes a moderate phase advance of about 1 h. Since the offset of activity occurs before the pulse, the effect will not be seen until Day 8. The advance will supplement the mouse's short FRP, causing the mouse's onset of activity to occur 1.5 h earlier than it did on Day 7. (Note: The dotted line in the left graphic shows when the onset of activity would have occurred if the pulse on Day 6 had not occurred.)</p></div></li><input type="radio" name="radio-btn" id="img-4" /><li class="slide-container"><div class="slide"><img src="http://ccb.ucsd.edu/_images/bioclock/EntrainmentSimulator/09_ZT22_05.JPG"><p><img src="http://ccb.ucsd.edu/_images/bioclock/EntrainmentSimulator/08_CaptionPRC02.png" style="max-width:150px;float:right;z-index:9; padding-left:10px;padding-right:1em;padding-bottom:2em;">''Day 8:'' The pulse now lands at about CT 1.5. As suggested by the PRC, this produces a phase advance of ~0.75 h. Since the offset of activity has already occurred before the pulse, this effect will not be seen until Day 9. The advance will supplement the mouse's short FRP, causing the onset of activity on Day 9 to occur ~1.25 h earlier than it did on Day 8. Note: The dotted line in the left graphic shows when activity would have begun on Day 8 if the pulse on Day 7 had not occurred.</p></div></li><input type="radio" name="radio-btn" id="img-5" /><li class="slide-container"><div class="slide"><img src="http://ccb.ucsd.edu/_images/bioclock/EntrainmentSimulator/09_ZT22_06.JPG"><p><img src="http://ccb.ucsd.edu/_images/bioclock/EntrainmentSimulator/08_CaptionPRC03.png" style="max-width:150px;float:right;z-index:9; padding-left:10px;padding-right:1em;padding-bottom:2em;">''Day 9:'' The pulse now lands at about CT 2.75. As suggested by the PRC, this produces a small phase advance of ~0.2 h. Since the offset of activity has already occurred before the pulse, this effect will not be seen until Day 10. The advance will supplement the mouse's short FRP, causing the onset of activity on Day 10 to occur ~0.7 h earlier than it did on Day 9. Note: The dotted line in the left graphic shows when activity would have begun on Day 9 if the pulse on Day 8 had not occurred.</p></div></li><input type="radio" name="radio-btn" id="img-6" /><li class="slide-container"><div class="slide"><img src="http://ccb.ucsd.edu/_images/bioclock/EntrainmentSimulator/09_ZT22_07.JPG"><p><img src="http://ccb.ucsd.edu/_images/bioclock/EntrainmentSimulator/08_CaptionPRC04.png" style="max-width:150px;float:right;z-index:9; padding-left:10px;padding-right:1em;padding-bottom:2em;">''Days 10-21:'' On Day 10, the pulse now lands at about CT 3.45. This is the Dead Zone of the PRC, and has no effect: the mouse free-runs. It takes many days for the the FRP to bring the mouse to a point where the light pulse is not landing in the Dead Zone.</p></div></li><input type="radio" name="radio-btn" id="img-7" /><li class="slide-container"><div class="slide"><img src="http://ccb.ucsd.edu/_images/bioclock/EntrainmentSimulator/09_ZT22_08.JPG"><p><img src="http://ccb.ucsd.edu/_images/bioclock/EntrainmentSimulator/08_CaptionPRC09.png" style="max-width:150px;float:right;z-index:9; padding-left:10px;padding-right:1em;padding-bottom:2em;">''Day 22:'' The pulse now lands at about CT 9.45. This produces a small phase delay of 0.35 h, which partially counteracts the short FRP so that the onset of activity on Day 22 occurs 0.15 h earlier than it did on Day 21.</p></div></li><input type="radio" name="radio-btn" id="img-8" /><li class="slide-container"><div class="slide"><img src="http://ccb.ucsd.edu/_images/bioclock/EntrainmentSimulator/09_ZT22_09.JPG" /><p><img src="http://ccb.ucsd.edu/_images/bioclock/EntrainmentSimulator/08_CaptionPRC09.png" style="max-width:150px;float:right;z-index:9; padding-left:10px;padding-right:1em;padding-bottom:2em;">''Day 23:'' The pulse now lands at about CT 9.6. This produces a small phase delay of ~0.4 h, which mostly counteracts the short FRP so that the onset of activity on Day 23 occurs 0.1 h earlier than it did on Day 22.</p></div></li><input type="radio" name="radio-btn" id="img-9" /><li class="slide-container"><div class="slide"><img src="http://ccb.ucsd.edu/_images/bioclock/EntrainmentSimulator/09_ZT22_10.JPG" /><p><img src="http://ccb.ucsd.edu/_images/bioclock/EntrainmentSimulator/08_CaptionPRC10.png" style="max-width:150px;float:right;z-index:9; padding-left:10px;padding-right:1em;padding-bottom:2em;">''Day 24:'' You get the idea: the pulse is landing increasingly closer to CT 10. When the pulse lands at CT 10, it will produce a phase delay of 0.5 h, which exactly counteracts the short FRP. As long as the light pulses remain in place, the onset of activity on every day after Day 24 will occur at exactly the same ZT that it did on day 24.</p></div></li><input type="radio" name="radio-btn" id="img-10" /><li class="slide-container"><div class="slide"><img src="http://ccb.ucsd.edu/_images/bioclock/EntrainmentSimulator/09_ZT22_11.jpg" /><p>''Phase Angle (Psi):'' The mouse entrains with repeated pulses so long as they land at CT 10. The entraining pulse occurs ~2 h before the onset of activity. We call the difference between these two values the "phase angle of entrainment," symbolized by the Greek letter psi (ψ). For this mouse, the phase angle of entrainment to a 24 h period is about 2 h. With the single-plotted actogram shown here, you might describe the phase angle by saying that activity onset occurs 22 h ''before'' the light pulse. This is technically correct. It is equivalent, however, to saying the light pulse falls 2 h before activity onset. Did you notice that in each example, the phase angle ends up being the same despite entrainment taking different routes and number of days to achieve steady state?</p></div></li><li class="nav-dots"><label for="img-1" class="nav-dot" id="img-dot-1"></label><label for="img-2" class="nav-dot" id="img-dot-2"></label><label for="img-3" class="nav-dot" id="img-dot-3"></label><label for="img-4" class="nav-dot" id="img-dot-4"></label><label for="img-5" class="nav-dot" id="img-dot-5"></label><label for="img-6" class="nav-dot" id="img-dot-6"></label><label for="img-7" class="nav-dot" id="img-dot-7"></label><label for="img-8" class="nav-dot" id="img-dot-8"></label><label for="img-9" class="nav-dot" id="img-dot-9"></label><label for="img-10" class="nav-dot" id="img-dot-10"></label></li></ul></div><<silently>><<repeat 1s>><<if setup.trim($Days) is $Correct1 || setup.trim(setup.GoBig($Days)) is $Correct1t>><<addclass "#Badge1" "check">><<removeclass "#Badge1" "qmark">><<removeclass "#Badge1" "ex">><<addclass "#Q1" "correct">><<removeclass "#Q1" "unknown">><<removeclass "#Q1" "wrong">><<elseif setup.trim($Days) isnot "" && setup.trim($Days) isnot "">><<addclass "#Badge1" "ex">><<removeclass "#Badge1" "qmark">><<removeclass "#Badge1" "check">><<addclass "#Q1" "wrong">><<removeclass "#Q1" "unknown">><<removeclass "#Q1" "correct">><<elseif setup.trim($Days) is "" || setup.trim($Days) is "">><<addclass "#Badge1" "qmark">><<removeclass "#Badge1" "check">><<removeclass "#Badge1" "ex">><<addclass "#Q1" "unknown">><<removeclass "#Q1" "correct">><<removeclass "#Q1" "wrong">><</if>><<if $obs is $Correct2>><<addclass "#Badge2" "check">><<removeclass "#Badge2" "qmark">><<removeclass "#Badge2" "ex">><<addclass "#Q2" "correct">><<removeclass "#Badge2" "unknown">><<elseif $obs isnot "empty">><<addclass "#Badge2" "ex">><<removeclass "#Badge2" "qmark">><<removeclass "#Badge2" "check">><<addclass "#Q2" "wrong">><<removeclass "#Q2" "unknown">><<removeclass "#Q2" "correct">><</if>><<if setup.trim($Psi) is $Correct3 || setup.trim(setup.GoBig($Psi)) is $Correct3t>><<addclass "#Badge3" "check">><<removeclass "#Badge3" "qmark">><<removeclass "#Badge3" "ex">><<addclass "#Q3" "correct">><<removeclass "#Q3" "unknown">><<removeclass "#Q3" "wrong">><<elseif setup.trim($Psi) isnot "" && setup.trim($Psi) isnot "">><<addclass "#Badge3" "ex">><<removeclass "#Badge3" "qmark">><<removeclass "#Badge3" "check">><<addclass "#Q3" "wrong">><<removeclass "#Q3" "unknown">><<removeclass "#Q3" "correct">><<elseif setup.trim($Psi) is "" || setup.trim($Psi) is "">><<addclass "#Badge3" "qmark">><<removeclass "#Badge3" "check">><<removeclass "#Badge3" "ex">><<addclass "#Q3" "unknown">><<removeclass "#Q3" "correct">><<removeclass "#Q3" "wrong">><</if>><<if (setup.trim($Days) is $Correct1 || setup.trim(setup.GoBig($Days)) is $Correct1t) && $obs is $Correct2 && (setup.trim($Psi) is $Correct3 || setup.trim(setup.GoBig($Psi)) is $Correct3t)>><<addclass ".gate" "open">><<removeclass ".gate" "closed">><<replace "#gate">><u>[[Proceed|ShortPeriod]]</u><</replace>><<elseif setup.trim($Days) isnot $Correct1 || setup.trim($Days) isnot $Correct1t ||$obs isnot $Correct2 || setup.trim($Psi) isnot $Correct3 || setup.trim($Psi) isnot $Correct3t>><<addclass ".gate" "closed">><<removeclass ".gate" "open">><<replace "#gate">>==Proceed==<</replace>><</if>><</repeat>><</silently>><span style="color:#223d8e;"> ''Entrainment I: Repeated pulses''</span>
While a single, acute light pulse can produce an interesting phase shift, the mouse will resume its free-running rhythm after the single pulse. But if we apply ''repeated'' light pulses every day, we can repeatedly phase-shift the mouse, forcing the mouse's activity rhythm out of the FRP and synchronizing its rhythms to the schedule we impose: that's ''entrainment''.
Since we're going to give repeated //Zeitgebers// (light pulses) on a regular interval, we now need to go back to using environmental time (not circadian time) in describing when the pulse occurs. We'll assume a ''Zeitgeber Time (ZT)'' of 24 normal hours. Just as circadian biologists use a lowercase tau (𝛕) to represent the period of Circadian Time, they use capital Tau (Τ) to represent the period of Zeitgeber Time. So, for the next few examples, 𝛕=23.5 and Τ=24 h.
We'll select a single hour each day to regularly provide the pulse. In the following passages, you'll explore what happens if we apply repeated pulses at ZT 6, ZT 14, and ZT 22. On each day, we will have to figure out when a light pulse at a particular ZT falls in Circadian Time -- and that CT is probably going to change from day to day until entrainment is achieved.
<u>[[Proceed|Disclaimers]]</u><span style="color:#223d8e;">''A Short FRP'' </span>
So far, we've been working with a wild-type mouse whose FRP is 23.5 h. Some mutations can alter FRP, and this in turn alters what kind of phase shift is required for entrainment.
Let's look first at a mouse with a very short FRP of 22 h. Notice how quickly the onsets of activity "drift" across the actogram:
<img src="http://ccb.ucsd.edu/_images/bioclock/EntrainmentSimulator/10_ShortFRP.gif" width="100%">
<span style="color:#223d8e;"><u>[[Proceed: Entrainment with a short FRP->ShortEntrain]]</u>.</span><<set $StackArray to [1,0,0,0,0,0,0,0,0,0,0,0,0,0,0,0,0,0,0,0,0,0,0,0]>><span style="color:#223d8e;"> ''Go ahead and play with acute light pulses at every phase of CT!''</span>
The mouse free-runs for 5 days before you apply your pulses. Use the yellow box on the slider to pick a time to give the pulse. You'll see the effects of your decision as you go. Feel free to <u>[[move on when you're done.->Q1]]</u>
<div class="flexrow"><div class="flexcolumn1"><div style="margin:auto; max-width:445px;"><img src="http://ccb.ucsd.edu/_images/bioclock/EntrainmentSimulator/07_SliderTop.png"></div><<set $InVar to 6>><div style="width:100%;margin:auto;text-align:center;"><<numberslider3 "$InVar" $InVar 1 24 1>></div><<repeat .05s>><<for _x to 0; _x lt $StackArray.length;_x++>><<if _x+1 is $InVar>><<set $StackArray[_x] to 1>><<else>><<set$StackArray[_x] to 0>><</if>><</for>><<if passage() is passage()>><<for _i to 0; _i lt $StackArray.length; _i++>><<set $Checker to "#e"+_i>><<set $CapCheck to "#c"+_i>><<if $StackArray[_i] is 1>><<removeclass $Checker "GoAway">><<removeclass $CapCheck "GoAway">><<for _j to 0; _j lt $StackArray.length; _j++>><<if _j isnot _i>><<set $Checker2 to "#e"+_j>><<set $CapCheck2 to "#c"+_j>><<addclass $Checker2 "GoAway">><<addclass $CapCheck2 "GoAway">><</if>><</for>><</if>><</for>><</if>><<set $Picker to $InVar-1>><<replace "#caption">><p style="line-height:1em;font-size:.9em;">$Caption[$Picker]</p><</replace>><</repeat>><div class="stacker" style="margin:auto;height:421px;"><div class="stack2 GoAway" id="e0"><img src="http://ccb.ucsd.edu/_images/bioclock/EntrainmentSimulator/07_Slider_CT01.png"></div><div class="stack2 GoAway" id="e1"><img src="http://ccb.ucsd.edu/_images/bioclock/EntrainmentSimulator/07_Slider_CT02.png"></div><div class="stack2 GoAway" id="e2"><img src="http://ccb.ucsd.edu/_images/bioclock/EntrainmentSimulator/07_Slider_CT03.png"></div><div class="stack2 GoAway" id="e3"><img src="http://ccb.ucsd.edu/_images/bioclock/EntrainmentSimulator/07_Slider_CT04.png"></div><div class="stack2 GoAway" id="e4"><img src="http://ccb.ucsd.edu/_images/bioclock/EntrainmentSimulator/07_Slider_CT05.png"></div><div class="stack2 GoAway" id="e5"><img src="http://ccb.ucsd.edu/_images/bioclock/EntrainmentSimulator/07_Slider_CT06.png"></div><div class="stack2 GoAway" id="e6"><img src="http://ccb.ucsd.edu/_images/bioclock/EntrainmentSimulator/07_Slider_CT07.png"></div><div class="stack2 GoAway" id="e7"><img src="http://ccb.ucsd.edu/_images/bioclock/EntrainmentSimulator/07_Slider_CT08.png"></div><div class="stack2 GoAway" id="e8"><img src="http://ccb.ucsd.edu/_images/bioclock/EntrainmentSimulator/07_Slider_CT09.png"></div><div class="stack2 GoAway" id="e9"><img src="http://ccb.ucsd.edu/_images/bioclock/EntrainmentSimulator/07_Slider_CT10.png"></div><div class="stack2 GoAway" id="e10"><img src="http://ccb.ucsd.edu/_images/bioclock/EntrainmentSimulator/07_Slider_CT11.png"></div><div class="stack2 GoAway" id="e11"><img src="http://ccb.ucsd.edu/_images/bioclock/EntrainmentSimulator/07_Slider_CT12.png"></div><div class="stack2 GoAway" id="e12"><img src="http://ccb.ucsd.edu/_images/bioclock/EntrainmentSimulator/07_Slider_CT13.png"></div><div class="stack2 GoAway" id="e13"><img src="http://ccb.ucsd.edu/_images/bioclock/EntrainmentSimulator/07_Slider_CT14.png"></div><div class="stack2 GoAway" id="e14"><img src="http://ccb.ucsd.edu/_images/bioclock/EntrainmentSimulator/07_Slider_CT15.png"></div><div class="stack2 GoAway" id="e15"><img src="http://ccb.ucsd.edu/_images/bioclock/EntrainmentSimulator/07_Slider_CT16.png"></div><div class="stack2 GoAway" id="e16"><img src="http://ccb.ucsd.edu/_images/bioclock/EntrainmentSimulator/07_Slider_CT17.png"></div><div class="stack2 GoAway" id="e17"><img src="http://ccb.ucsd.edu/_images/bioclock/EntrainmentSimulator/07_Slider_CT18.png"></div><div class="stack2 GoAway" id="e18"><img src="http://ccb.ucsd.edu/_images/bioclock/EntrainmentSimulator/07_Slider_CT19.png"></div><div class="stack2 GoAway" id="e19"><img src="http://ccb.ucsd.edu/_images/bioclock/EntrainmentSimulator/07_Slider_CT20.png"></div><div class="stack2 GoAway" id="e20"><img src="http://ccb.ucsd.edu/_images/bioclock/EntrainmentSimulator/07_Slider_CT21.png"></div><div class="stack2 GoAway" id="e21"><img src="http://ccb.ucsd.edu/_images/bioclock/EntrainmentSimulator/07_Slider_CT22.png"></div><div class="stack2 GoAway" id="e22"><img src="http://ccb.ucsd.edu/_images/bioclock/EntrainmentSimulator/07_Slider_CT23.png"></div><div class="stack2 GoAway" id="e23"><img src="http://ccb.ucsd.edu/_images/bioclock/EntrainmentSimulator/07_Slider_CT24.png"></div></div></div><div class="flexcolumn2"><div class="stacker" style="margin:auto; height:124px; width:175px;"><div class="stack GoAway" id="c0"><img src="http://ccb.ucsd.edu/_images/bioclock/EntrainmentSimulator/08_CaptionPRC01.png" style="margin:auto;"></div><div class="stack GoAway" id="c1"><img src="http://ccb.ucsd.edu/_images/bioclock/EntrainmentSimulator/08_CaptionPRC02.png" style="margin:auto;"></div><div class="stack GoAway" id="c2"><img src="http://ccb.ucsd.edu/_images/bioclock/EntrainmentSimulator/08_CaptionPRC03.png" style="margin:auto;"></div><div class="stack GoAway" id="c3"><img src="http://ccb.ucsd.edu/_images/bioclock/EntrainmentSimulator/08_CaptionPRC04.png" style="margin:auto;"></div><div class="stack GoAway" id="c4"><img src="http://ccb.ucsd.edu/_images/bioclock/EntrainmentSimulator/08_CaptionPRC05.png" style="margin:auto;"></div><div class="stack GoAway" id="c5"><img src="http://ccb.ucsd.edu/_images/bioclock/EntrainmentSimulator/08_CaptionPRC06.png" style="margin:auto;"></div><div class="stack GoAway" id="c6"><img src="http://ccb.ucsd.edu/_images/bioclock/EntrainmentSimulator/08_CaptionPRC07.png" style="margin:auto;"></div><div class="stack GoAway" id="c7"><img src="http://ccb.ucsd.edu/_images/bioclock/EntrainmentSimulator/08_CaptionPRC08.png" style="margin:auto;"></div><div class="stack GoAway" id="c8"><img src="http://ccb.ucsd.edu/_images/bioclock/EntrainmentSimulator/08_CaptionPRC09.png" style="margin:auto;"></div><div class="stack GoAway" id="c9"><img src="http://ccb.ucsd.edu/_images/bioclock/EntrainmentSimulator/08_CaptionPRC10.png" style="margin:auto;"></div><div class="stack GoAway" id="c10"><img src="http://ccb.ucsd.edu/_images/bioclock/EntrainmentSimulator/08_CaptionPRC11.png" style="margin:auto;"></div><div class="stack GoAway" id="c11"><img src="http://ccb.ucsd.edu/_images/bioclock/EntrainmentSimulator/08_CaptionPRC12.png" style="margin:auto;"></div><div class="stack GoAway" id="c12"><img src="http://ccb.ucsd.edu/_images/bioclock/EntrainmentSimulator/08_CaptionPRC13.png" style="margin:auto;"></div><div class="stack GoAway" id="c13"><img src="http://ccb.ucsd.edu/_images/bioclock/EntrainmentSimulator/08_CaptionPRC14.png" style="margin:auto;"></div><div class="stack GoAway" id="c14"><img src="http://ccb.ucsd.edu/_images/bioclock/EntrainmentSimulator/08_CaptionPRC15.png" style="margin:auto;"></div><div class="stack GoAway" id="c15"><img src="http://ccb.ucsd.edu/_images/bioclock/EntrainmentSimulator/08_CaptionPRC16.png" style="margin:auto;"></div><div class="stack GoAway" id="c16"><img src="http://ccb.ucsd.edu/_images/bioclock/EntrainmentSimulator/08_CaptionPRC17.png" style="margin:auto;"></div><div class="stack GoAway" id="c17"><img src="http://ccb.ucsd.edu/_images/bioclock/EntrainmentSimulator/08_CaptionPRC18.png" style="margin:auto;"></div><div class="stack GoAway" id="c18"><img src="http://ccb.ucsd.edu/_images/bioclock/EntrainmentSimulator/08_CaptionPRC19.png" style="margin:auto;"></div><div class="stack GoAway" id="c19"><img src="http://ccb.ucsd.edu/_images/bioclock/EntrainmentSimulator/08_CaptionPRC20.png" style="margin:auto;"></div><div class="stack GoAway" id="c20"><img src="http://ccb.ucsd.edu/_images/bioclock/EntrainmentSimulator/08_CaptionPRC21.png" style="margin:auto;"></div><div class="stack GoAway" id="c21"><img src="http://ccb.ucsd.edu/_images/bioclock/EntrainmentSimulator/08_CaptionPRC22.png" style="margin:auto;"></div><div class="stack GoAway" id="c22"><img src="http://ccb.ucsd.edu/_images/bioclock/EntrainmentSimulator/08_CaptionPRC23.png" style="margin:auto;"></div><div class="stack GoAway" id="c23"><img src="http://ccb.ucsd.edu/_images/bioclock/EntrainmentSimulator/08_CaptionPRC24.png" style="margin:auto;"></div></div><span id="caption">Test2</span></div></div><<set $Caption to ["A pulse at CT 1 causes a phase ''advance'' of about 1 h on Day 6.\n\nActivity begins ''1.5 h earlier'' than it did on Day 5: the mouse's free-running period would have naturally caused activity to begin 0.5 h earlier, and in addition to that, we have caused a 1 h advance.","A pulse at CT 2 causes a phase ''advance'' of about 0.5 h (30 minutes) on Day 6.\n\nActivity begins ''1 h earlier'' than it did on Day 5: the mouse's free-running period would have naturally caused activity to begin .5 h earlier, and in addition to that, we have caused a 0.5 h advance.","A pulse at CT 3 causes a tiny phase ''advance'' of about 0.25 h (15 minutes) on Day 6.\n\nActivity begins ''45 minutes earlier'' than it did on Day 5: the mouse's free-running period would have naturally caused activity to begin ~30 minutes earlier, and in addition to that, we have caused a 15 minute advance.","A pulse at CT 4 has ''no effect'': this is the \"Dead Zone\" of the PRC.\n\nThe mouse does begin its activity 0.5 h earlier on Day 6 than it did on Day 5, but this is NOT a phase shift: it simply reflects the mouse's short FRP of 23.5 h.","A pulse at CT 5 has ''no effect'': this is the \"Dead Zone\" of the PRC.\n\nThe mouse does begin its activity 0.5 h earlier on Day 6 than it did on Day 5, but this is NOT a phase shift: it simply reflects the mouse's short FRP of 23.5 h.","A pulse at CT 6 has ''no effect'': this is the \"Dead Zone\" of the PRC.\n\nThe mouse does begin its activity 0.5 h earlier on Day 6 than it did on Day 5, but this is NOT a phase shift: it simply reflects the mouse's short FRP of 23.5 h.","A pulse at CT 7 has ''no effect'': this is the \"Dead Zone\" of the PRC.\n\nThe mouse does begin its activity 0.5 h earlier on Day 6 than it did on Day 5, but this is NOT a phase shift: it simply reflects the mouse's short FRP of 23.5 h.","A pulse at CT 8 has ''no effect'': this is the \"Dead Zone\" of the PRC.\n\nThe mouse does begin its activity 0.5 h earlier on Day 6 than it did on Day 5, but this is NOT a phase shift: it simply reflects the mouse's short FRP of 23.5 h.","A pulse at CT 9 causes a tiny phase ''delay'' of about 0.25 h (15 minutes) on Day 6.\n\nActivity begins ''15 minutes earlier'' than it did on Day 5: the mouse's free-running period would have naturally caused activity to begin ~30 minutes earlier, and our light pulse has only partially counteracted that by causing a ~15 minute delay.","A pulse at CT 10 causes a slightly larger phase ''delay'' of about 0.5 h (30 minutes) on Day 6.\n\nActivity begins ''no later than'' it did on Day 5: the mouse's free-running period would have naturally caused activity to begin ~30 minutes earlier, and our light pulse has counteracted that. The two effects cancel each other out.","A pulse at CT 11 causes a slightly larger phase ''delay'' of about 0.75 h (45 minutes) on Day 6.\n\nActivity begins about ''0.25 h later'' than it did on Day 5: the mouse's free-running period would have naturally caused activity to begin ~30 minutes earlier. Our light pulse has counteracted this with a ~45 minute delay. The effect of the pulse overshadows the FRP, resulting in an overall phase delay.","A pulse at CT 12 causes a larger phase ''delay'' of about 1.75 h (1 h + 45 m on Day 6.\n\nActivity begins about ''1.25 h later'' than it did on Day 5: the mouse's free-running period would have naturally caused activity to begin ~30 minutes earlier, but our light pulse has counteracted that. The effect of the pulse overshadows the FRP, resulting in an overall phase delay.","A pulse at CT 13 causes a significant phase ''delay'' of about 2 h.\n\n''Note:'' Since we administer our light pulse after the onset of activity on Day 6, the initial effect is mainly seen by how the ''offset'' of activity on Day 6 has been delayed.\n\nActivity on Day 7 begins about ''1.5 h later'' than it did on Day 6: the mouse's free-running period would have naturally caused activity to begin ~30 minutes earlier, but our light pulse has counteracted that. The effect of the pulse overshadows the FRP, resulting in an overall phase delay.","A pulse at CT 14 causes a large phase ''delay'' of about 3 h.\n\n''Note:'' Since we administer our light pulse after the onset of activity on Day 6, the initial effect is mainly seen by how the ''offset'' of activity on Day 6 has been delayed.\n\nActivity on Day 7 begins about ''2.5 h later'' than it did on Day 6: the mouse's free-running period would have naturally caused activity to begin ~30 minutes earlier, but our light pulse has counteracted that. The effect of the pulse overshadows the FRP, resulting in an overall phase delay.","A pulse at CT 15 causes the ''largest possible phase delay'' of about 4 h.\n\n''Note:'' Since we administer our light pulse after the onset of activity on Day 6, the initial effect is mainly seen by how the ''offset'' of activity on Day 6 has been delayed.\n\nActivity on Day 7 begins about ''3.5 h later'' than it did on Day 6: the mouse's free-running period would have naturally caused activity to begin ~30 minutes earlier, but our light pulse has counteracted that. The effect of the pulse overshadows the FRP, resulting in an overall phase delay.","A pulse at CT 16 causes a large phase ''delay'' of about 3 h.\n\n''Note:'' Since we administer our light pulse after the onset of activity on Day 6, the initial effect is mainly seen by how the ''offset'' of activity on Day 6 has been delayed.\n\nActivity on Day 7 begins about ''2.5 h later'' than it did on Day 6: the mouse's free-running period would have naturally caused activity to begin ~30 minutes earlier, but our light pulse has counteracted that. The effect of the pulse overshadows the FRP, resulting in an overall phase delay.","A pulse at CT 17 causes a large phase ''advance'' of about 1 h.\n\n''Note:'' Since we administer our light pulse after the onset of activity on Day 6, the initial effect is mainly seen by how the ''offset'' of activity on Day 6 has been advanced.\n\nActivity on Day 7 begins about ''1.5 h earlier'' than it did on Day 6: the mouse's free-running period would have naturally caused activity to begin ~30 minutes earlier, and our light pulse has added an additional 1 h advance.","A pulse at CT 18 causes a large phase ''advance'' of about 2 h.\n\n''Note:'' Since we administer our light pulse after the onset of activity on Day 6, the initial effect is mainly seen by how the ''offset'' of activity on Day 6 has been advanced.\n\nActivity on Day 7 begins about ''2.5 h earlier'' than it did on Day 6: the mouse's free-running period would have naturally caused activity to begin ~30 minutes earlier, and our light pulse has added an additional 2 h advance.","A pulse at CT 19 causes ''the largest possible phase advance'' of about 2.25 h (2 h + 15 m).\n\n''Note:'' Since we administer our light pulse after the onset of activity on Day 6, the initial effect is mainly seen by how the ''offset'' of activity on Day 6 has been advanced.\n\nActivity on Day 7 begins about ''2.75 h earlier'' than it did on Day 6: the mouse's free-running period would have naturally caused activity to begin ~30 minutes earlier, and our light pulse has added an additional 2.25 h advance.","A pulse at CT 20 causes a large phase ''advance'' of about 2 h.\n\n''Note:'' Since we administer our light pulse after the onset of activity on Day 6, the initial effect is mainly seen by how the ''offset'' of activity on Day 6 has been advanced.\n\nActivity on Day 7 begins about ''2.5 h earlier'' than it did on Day 6: the mouse's free-running period would have naturally caused activity to begin ~30 minutes earlier, and our light pulse has added an additional 2 h advance.","A pulse at CT 21 causes a phase ''advance'' of about 1.75 h (1 h + 45 m).\n\n''Note:'' Since we administer our light pulse after the onset of activity on Day 6, the initial effect is mainly seen by how the ''offset'' of activity on Day 6 has been advanced.\n\nActivity on Day 7 begins about ''2.25 h earlier'' than it did on Day 6: the mouse's free-running period would have naturally caused activity to begin ~30 minutes earlier, and our light pulse has added an additional 1.75 h advance.","A pulse at CT 22 causes a phase ''advance'' of about 1.5 h (1 h + 30 m).\n\n''Note:'' Since we administer our light pulse after the onset of activity on Day 6, the initial effect is mainly seen by how the ''offset'' of activity on Day 6 has been advanced.\n\nActivity on Day 7 begins about ''2 h earlier'' than it did on Day 6: the mouse's free-running period would have naturally caused activity to begin ~30 minutes earlier, and our light pulse has added an additional 1.5 h advance.","A pulse at CT 23 causes a phase ''advance'' of about 1.25 h (1 h + 15 m).\n\n''Note:'' Since we administer our light pulse after the onset of activity on Day 6, the initial effect is mainly seen by how the ''offset'' of activity on Day 6 has been advanced.\n\nActivity on Day 7 begins about ''1.75 h earlier'' than it did on Day 6: the mouse's free-running period would have naturally caused activity to begin ~30 minutes earlier, and our light pulse has added an additional 1.25 h advance.","A pulse at CT 24 causes a phase ''advance'' of about 1 h.\n\n''Note:'' Since we administer our light pulse after the onset of activity on Day 6, the initial effect is mainly seen by how the ''offset'' of activity on Day 6 has been advanced.\n\nActivity on Day 7 begins about ''1.5 h earlier'' than it did on Day 6: the mouse's free-running period would have naturally caused activity to begin ~30 minutes earlier, and our light pulse has added an additional 1 h advance."]>><span style="color:#223d8e;">''Entrainment with a short FRP'' </span>
We can actually predict how our mouse will entrain using the PRC.<p>To counteract the mouse's short FRP (𝛕) of 22 h and entrain it to a Zeitgeber period (Τ) of 24 h, we need a regular phase shift to stretch the cycle to 24 h. A phase shift is represented using "ΔΦ" (delta phi). To find the desired phase shift for entrainment, the formula is: </p><p style="line-height:1.1em;margin:auto 2em auto 2em;"><span style="color:blue;">𝛕 - Τ = ΔΦ</span></p><p>In this case:</p><p style="line-height:1.1em;margin:auto 2em auto 2em;">22 h - 24 h = -2 h</p><div class="flexrow"><div class="flexcolumn"><p>Where the ''negative'' value for ΔΦ indicates that a phase ''delay'' is what we need. As indicated on the PRC, such a phase delay of 2 h is caused by a pulse delivered at CT 13 -- ''one hour'' after the onset of activity. (Remember, we cannot use the steep positive slope of the PRC for entrainment).</p></div><div class="flexcolumn"><p><img src="http://ccb.ucsd.edu/_images/bioclock/EntrainmentSimulator/08_CaptionPRC13.png" style="max-width:250px;"></p></div></div><div class="flexrow"><div class="flexcolumn"><div class="flexrow"><div class="flexcolumn"><p>So, we can predict that the phase angle of entrainment (ψ) will be -1 h: our mouse with an FRP of 22 h will entrain when our regular pulse of light is landing 1 h after the onset of activity. This is indicated in the actogram.</p><p>[[Move On|LongPeriod]]</p></div><div class="flexcolumn"><p><img src="http://ccb.ucsd.edu/_images/bioclock/EntrainmentSimulator/10_ShortZT6.png" style="max-width:250px;"></p></div></div><span style="color:#223d8e;">''Entrainment with a long FRP'' </span>
We can again predict how our mouse will entrain using the PRC.<p>To counteract the mouse's long FRP (𝛕) of 24.5 h and entrain it to a Zeitgeber period (Τ) of 24 h, we need a regular phase shift to compress the cycle to 24 h. Let's return to our formula to determine the phase shift needed: </p><p style="line-height:1.1em;margin:auto 2em auto 2em;"><span style="color:blue;">𝛕 - Τ = ΔΦ</span></p><p>In this case:</p><p style="line-height:1.1em;margin:auto 2em auto 2em;">24.5 h - 24 h = 0.5 h</p><div class="flexrow"><div class="flexcolumn"><p>Where the ''positive'' value for ΔΦ means that a phase ''advance'' is what we need. As indicated on the PRC, such a phase advance of 0.5 h is caused by a pulse delivered at CT 2 -- ''10 hours'' before the onset of activity. (Remember, we cannot use the steep positive slope of the PRC for entrainment).</p></div><div class="flexcolumn"><p><img src="http://ccb.ucsd.edu/_images/bioclock/EntrainmentSimulator/08_CaptionPRC02.png" style="max-width:250px;"></p></div></div><div class="flexrow"><div class="flexcolumn"><div class="flexrow"><div class="flexcolumn"><p>So, we can predict that the phase angle of entrainment (ψ) will be 10 h: our mouse with an FRP of 24.5 h will entrain when our regular pulse of light is landing 10 h before the onset of activity. This is indicated in the actogram.</p><p>[[Move On|Limits]].</p></div><div class="flexcolumn"><p><img src="http://ccb.ucsd.edu/_images/bioclock/EntrainmentSimulator/10_LongZT6.png" style="max-width:250px;"></p></div></div><span style="color:#223d8e;"> ''Disclaimers''</span>
Before we experiment with repeated light pulses, let's clarify 2 things.
''First'', the graphics and examples that follow are idealizations. In reality light pulses' effects can sometimes take a few days to fully appear. There will often be "transient cycles" where the onset of activity may not fully reflect the phase shift that was caused by the pulse. Here we ignore transient cycles, and pretend that the effects of a pulse are seen immediately.
''Second'', we should clarify one final detail about the PRC, concerning the steep positive slope between CT 16 and CT 18, highlighted in red below:
<img src="http://ccb.ucsd.edu/_images/bioclock/EntrainmentSimulator/06_PrcExtra2.jpg" style="max-width:409px;height:auto;">
<p style="line-height:1.1em;margin:auto 2em auto 2em;"><span style="color:red;">''Unstable Results:''</span>
Single light pulses applied in this region can produce phase shifts; however, trying to use repeated light pulses to produce repeated effects is unstable. (In this part of the PRC, any error in entrainment results in larger deviations on subsequent days. In other parts of the PRC, any error in entrainment automatically corrects itself on subsequent days.) As a result, repeated pulses are not typically applied during these phases of CT to try to produce entrainment.</p>
''In other words:'' if you want to entrain an organism using repeated pulses of light, you'll want to avoid providing pulses in this region of the PRC. None of the examples that follow will try to use this region of the PRC.
Ready to <u>[[get started|ZT6]]</u>?''Version 2.0, completed September 12 2019''
Hi there, I'm Ben.
Starting from the original build that had been produced in the Winter 2019 BioClock Studio, I did most of the graphic re-design, Twine re-organization/"programming," and re-writing to wrap up the Entrainment Simulator in the Summer of 2019. I had lots of help from Karen Tonsfeldt and Michael Gorman.
I assume you're fiddling with the source files to (a) add something, or (b) try to reproduce an effect. Don't hesitate to email me (ben.sheredos@gmail.com). I'd be happy to help.
I'll offer a few quick notes.
*I tried to clean up the CSS and JS for the Twine, but may have failed for CSS. A lot of CSS stuff was there when I started and I don't know what it does, so I didn't delete it.
*Documentation in the CSS tries to explain what each chunk of CSS styling is doing, and also includes some notes about why we designed some passages the way we did.
*The "StoryBanner" box on the left of the Twinemap handles the BCS logo in the left navigation panel.
*The "StoryCaption" box on the left of the Twinemap handles the quick links in the left navigation panel.
*By default, Twine tries to preserve any whitespace you leave in when you write out a passage. This means that to remove whitespace on the user's side, you have to remove all whitespace on the backend: lots of plaintext, html, CSS, Twine functions, etc, have to be stacked up on a single line to avoid unwanted whitespace, making it very difficult to navigate if you're trying to edit a passage. Sorry. Best options are either (a) add linebreaks if you want to work on something, but remove them later, or (b) copy-paste out of twine into some other text editor, add linebreaks to follow the logic of a passage, then implement edits by finding the corresponding chunk of text in the passage in Twine.<span style="color:#223d8e;"> ''Predicting Possible and Impossible Entrainment'' </span>
<p>You're now familiar with a three-step "recipe" for predicting the phase angle of entrainment (ψ) for any FRP and for any regular Zeitgeber period:</p><p>''Step 1:'' solve for ΔΦ (delta phi):</p><p style="line-height:1.1em;margin:auto 2em auto 2em;"><span style="color:blue;">𝛕 - Τ = ΔΦ</span></p><p>(where 𝛕= the organism's FRP,
and Τ = the period of ZT to which we want to entrain the organism).</p><div class="flexrow"><div class="flexcolumn"><p>''Step 2:'' Using the PRC, locate the phase of CT at which the pulse must be delivered to produce ΔΦ (ignoring the steep positive slope of the PRC).</p></div><div class="flexcolumn"><p><img src="http://ccb.ucsd.edu/_images/bioclock/EntrainmentSimulator/06_FullPrcNoPulses.png" style="max-width:250px;"></p></div></div><p>''Step 3:'' Use a point of reference like onset of activity to calculate ψ. E.g.: if we use onset of activity in a nocturnal organism (CT 12) as our point of reference, and if ΔΦ is produced by repeated pulses at CT 10, then ψ = 2 h.
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<p>''<span style="color:red;">//Importantly//</span>, understanding this recipe can also let us predict the limits of possible entrainment.''</p><p>For example, the largest possible phase delay on this PRC is -4 h. Thus, we can never produce a ΔΦ beyond -4 using an acute pulse of light.</p><p>As a result, it will not be possible to entrain our wild-type mouse (with 𝛕 =23.5 h) to a very long Zeitgeber period where Τ = 29 h. Schematically, the longest possible Zeitgeber period to which an organism can be entrained is determined by this formula:</p><p style="line-height:1.1em;margin:auto 2em auto 2em;"><span style="color:blue;">𝛕 - ΔΦ<sub>maxDelay</sub> = T<sub>maxPeriod</sub></span></p><p>In this case:</p><p style="line-height:1.1em;margin:auto 2em auto 2em;">23.5 h + 4 h = 27.5 h </p><p>In other words: we cannot use repeated, acute light pulses to entrain our wild-type mouse to any very long Zeitgeber period where Τ is >27.5 h.</p><p>Similarly, we can predict the shortest possible Zietgeber period to which an organism can entrain:</p><p style="line-height:1.1em;margin:auto 2em auto 2em;"><span style="color:blue;">𝛕 - ΔΦ<sub>maxAdvance</sub> = T<sub>minPeriod</sub></span></p><p>In this case, the largest possible phase advance on the PRC is +2.25 h, and we can never produce a ΔΦ greater than +2.25. So:</p><p style="line-height:1.1em;margin:auto 2em auto 2em;">23.5 h - 2.25 h = 21.25 h </p><p>In other words: we cannot use repeated, acute light pulses to entrain our wild-type mouse to any very short period where Τ is <21.25 h.</p>
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[[What's next?|SkeletonPhotoperiod]]<span style="color:#223d8e;"> ''Skeleton Photoperiod'' </span>
<p>We have explored how a single light pulse was capable of entraining the mouse. Now, what would happen if there were two light pulses instead of only one?
In general, two pulses will have additive effects that are predictable based on the PRC. For example, if one pulse would cause a 3 h delay and the second would cause a 2 h advance, their combined effect would be a 1 h delay.
We will now show you an interesting phenomenon of a mouse entraining to two specially timed light pulses known as a skeleton photoperiod. In a skeleton photoperiod, the delay induced by the evening pulse and the advance from the morning pulse add up to produce the total phase shift necessary to entrain to 24 h.
Click through the images below (using the dots at the top) for an explanation. This is the last component of the Entrainment Simulator, so after you've clicked through, [[you're all done!|End]]
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<div style="width:100%;"><ul class="slides" style="display:block;"><input type="radio" name="radio-btn" id="img-1" checked /><li class="slide-container"><div class="slide"><img src="http://ccb.ucsd.edu/_images/bioclock/EntrainmentSimulator/11_Skel1.JPG" /><p>''Days 1-4:'' We can see a familiar actogram of a mouse free running in a constant darkness with its typical short FRP.</p></div></li><input type="radio" name="radio-btn" id="img-2" /><li class="slide-container"><div class="slide"><img src="http://ccb.ucsd.edu/_images/bioclock/EntrainmentSimulator/11_Skel2.JPG" /><p>''Day 5: '' We have given two separate 1 h light pulses to the mouse at two time points: one 1 h before the start of subjective night (ZT8, here approximately 1 h before the start of subjective night (CT11), and one 12 h later (CT 24/0). Let’s see what happens to the animal’s activity with this type of zeitgeber over the days that follow.</p>
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</div></li><input type="radio" name="radio-btn" id="img-3" /><li class="slide-container"><div class="slide"><img src="http://ccb.ucsd.edu/_images/bioclock/EntrainmentSimulator/11_Skel3.JPG" /><p>''Day 6-10:'' The mouse has successfully been entrained to a 24 h rhythm by these two separate light pulses!</p><p><span style="color:red;">NOTE</span>: Do you see anything special about the actogram? What about the timing of the light pulses in the figure? Click the LAST BUTTON.</p></div></li><input type="radio" name="radio-btn" id="img-4" /><li class="slide-container"><div class="slide"><img src="http://ccb.ucsd.edu/_images/bioclock/EntrainmentSimulator/11_Skel4.JPG" /><p>''Day 10:'' We have added a second actogram underneath with a LD 12:12 cycle. Compare the two. The activity of the mouse in the skeleton photoperiod actually looks similar to what activity would look like under a light/dark cycle with a full 12 h light phase, but it does so without the entire light phase!</p><p>How is this possible and what does this mean?</p><p>Under constant darkness, the mouse has entrained the two light pulses as if they were the signals for dusk and dawn! This means that, for this nocturnal rodent, the light between the pulses is not necessary (or even very important) for entrainment, and that the two light cues at dusk and dawn are strong enough Zeitgebers to entrain the animal. This type of entrainment, accomplished by light pulses causing acute phase shifts, is called ''non-parametric'' entrainment, and is typical of nocturnal animals that are exposed to relatively brief pulses at dusk and dawn (when they begin and end nighttime activity, respectively). In other organisms, including those that are diurnal, actions of light throughout the day may also contribute to entrainment. Such entrainment may involve changes in period (as well as phase shifts) and is called ''parametric'' entrainment.
</p></div></li>
<li class="nav-dots"><label for="img-1" class="nav-dot" id="img-dot-1"></label><label for="img-2" class="nav-dot" id="img-dot-2"></label><label for="img-3" class="nav-dot" id="img-dot-3"></label><label for="img-4" class="nav-dot" id="img-dot-4"></label></li></ul></div><span style="color:#223d8e;">''The Light Dark Actogram'' </span>
Before we proceed, we'll quickly review one important thing that will recur throughout the simulation.
An Actogram is a graphical representation of an organism’s activity and rest patterns. It enables us to draw conclusions about the internal circadian clock residing in an animal’s brain. An example is shown below:
<div style="width:50%; margin:auto;"><img src="http://ccb.ucsd.edu/_images/bioclock/EntrainmentSimulator/00_ActoRev.gif"></div>
At the very top of the actogram is a ''light/dark'' schedule, labelled "LD 12:12" and symbolized by the white and black bars. This type of schedule is pretty similar to what most of us experience daily, with a long, continuous period of 12 h of light followed by a long, continuous period of 12 h of darkness. The white parts of the bar on top represent light, and the black part represents darkness. Later on in the entrainment simulator, you’ll see some light/dark schedules that are ''all black'' to represent constant darkness, a lighting condition used frequently in the laboratory when studying circadian rhythms.
Underneath the light/dark schedule, the dark gray bars on each row represent an animal's locomotor activity over the course of one day. In this case, note that the activity coincides with the dark phase of the light/dark schedule: this animal is nocturnal.
To learn more about actograms, you can <a href="https://www.youtube.com/watch?v=jkdiis6o5dc" target="blank">watch the BioClock Studio’s video on understanding the actogram</a>.
<span style="color:#223d8e;"><u>[[Proceed: entrainment->ENTER]]</u></span>