BioSci 24237 BIOLOGICAL RHYTHMS AND SLEEP

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BioSci 24237BIOLOGICAL RHYTHMS AND SLEEP

• CLASS 3
• Circadian Rhythms Basic Properties
• January 14, 2002

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FREE-RUNNING RHYTHM OF LOCOMOTOR ACTIVITY IN A
HAMSTER
TIME OF DAY
1992
0
12
0
12
0
4/18
4/22
4/27
5/02
5/07
5/12
5/17
5/22
5/27
DATE
6/01
6/06
6/11
6/16
6/21
6/26
7/01
7/06
7/11
7/16
7/21
Turek, F.W., Van Reeth, O. (1996).
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Endogenous Nature of Circadian Rhythmicity

• Rodents housed under constant conditions in
  separate cages in the immediate vicinity of each
  other free-run with different periods
• Genetic mutations can alter the endogenous period
• Circadian rhythms develop normally in successive
  generations of organisms kept under constant
  conditions.

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Longitudinal record of wheel-running activity in
a hamster
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Free-run and re-entrainment of the human
sleep-wake cycle
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Entrainment

• The endogenous pacemaker needs to be synchronized
  to the 24-h day
• Environmental stimuli serve as entraining agents
  or zeitgebers
• The main zeitgeber is the light-dark cycle the
  formal properties of the response of the
  circadian pacemaker to light are the same for all
  species
• There are also non-photic zeitgebers but they are
  species-dependent
• The endogenous pacemaker has a certain inertia,
  hence the problems of jet lag and maladaptation
  to shift work

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Circadian phase shifts
(earlier timing)
(later timing)
Assumption shift of central circadian pacemaker
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Start constant conditions (DD)
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Shifting the rhythm of locomotor activity of a
hamster with exposure to light pulses
15-min light pulse
15-min light pulse
CT12 start of active period
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The Phase Response Curve to Light in rodents
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advance (earlier)
Light pulse
Phase shift (hrs)
0
delay (later)
-2
0
6
12
18
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Circadian Time
A phase-response curve (PRC) describes phase
shifts of circadian phase at all circadian times
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THE PHASE RESPONSE CURVE TO LIGHT
Czeisler, Richardson, Coleman, Zimmerman,
Moore-Ede, Dement Weitzman (1981).
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Human Phase Response Curve to Light
Light at sunrise/start of the day Phase advance -
clocks speeds up
Light at sunset/end of the day Phase delay -
clocks slows down
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CONCEPT OF ENTRAINMENT The endogenous period
Tau is not exactly equal to 24 hours. If Tau is
longer than 24 hours, e.g. Tau 25 hours, then
every day an advance phase shift of 1 hour needs
to be achieved The clock needs to speed
up. If Tau is shorter than 24 hours, e.g. Tau
23 hours, then every day a delay phase shift of
1 hour needs to be achieved The clock needs to
slow down.
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Consecutive phase shifts to light result in
re-entrainment of circadian rhythms
c
LD cycle shift
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Human Phase Response Curve to Light (Harvard)
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THE PHASE RESPONSE CURVE TO LIGHT
6 am
Czeisler, Richardson, Coleman, Zimmerman,
Moore-Ede, Dement Weitzman (1981).
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Light phase shifts human rhythms at all circadian
phases
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The magnitude of the phase shift induced by light
depends on light intensity
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Non-photic entrainment

• Studies in rodents have indicated that stimuli
  that increase activity during the usual rest
  period or that inhibit activity (force rest)
  during the usual active period are able to shift
  the clock
• The direction and magnitude of these non-photic
  shifts vary according to timing of exposure to
  the stimuli

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Shifting the rhythm of locomotor activity of a
hamster by inducing a pulse of activity at a
usual time of rest (here, using triazolam
injections)
Triazolam injection
Triazolam injection
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Phase Response Curves in rodents
Light
c
2
advance (earlier)
Phase shift (hrs)
0
delay (later)
-2
Normal active period
0
6
12
18
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Circadian Time
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Adaptation to a shift of light-dark cycle in a
hamster can be accelerated by the presentation
of a novel stimulus ( a new running wheel)
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Scheduled access to a running wheel in a mouse
can entrain the rhythm of locomotor activity
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Scheduled access to a running wheel in a mouse
can entrain the drinking rhythm
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Limits of entrainment

• Entrainment to T 28 hours is
  not possible
• Within the limits of entrainment, the intensity
  of zeitgeber exposure modulates ability to
  entrain
• Entrainment may be facilitated if the change in T
  is imposed gradually rather than abruptly

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Interactions between photic and non-photic
entrainment

• Linear/additive ?
• Synergetic ?
• What is the potential for accelerating adaptation
  to time shifts (jet lag, shift work)

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Circadian timing of exercise
Exercise timing n Morning (1000) 7 Afternoon
(1330) 7 Evening (1800) 6 Nocturnal
(0100) 8 Control 9
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The human Phase Response Curve to exercise
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04
10
16
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Approximate clock time
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The human Phase Response Curve to exercise

• Exercise in the early evening will advance the
  circadian clock (? Advance sleep propensity )
• Exercise in the late evening and at night will
  delay the circadian clock (? Delay sleep
  propensity )
• Exercise during the daytime has no
  detectable/consistent phase shifting effect

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Entrainment by food availability
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Evidence for entrainment by timing of food
presentation
Beginning/end of food deprivation
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The Circadian System