Circadian Rhythm Flashcards
what are actograms?
graphical representations used in circadian rhythm research to visualize activity patterns over time
what do actograms typically show?
- x-axis: time (hrs or days)
- y-axis: activity level (quantified and plotted as counts per time)
- data points: represents the activity level at the specific time (i.e., wheel rotations)
what are entrainments?
show how an organism’s activity rhythm synchronizes with external cues such as light-dark cycles, feeding times, or temperature changes.
When an organism’s activity rhythm is synchronized with an external cue, it demonstrates a stable and predictable pattern over time.
how could an actogram provide evidence for a self-sustaining endogenous circadian pacemaker?
- Free-Running Rhythm: In the absence of external time cues (such as light-dark cycles), the organism should continue to exhibit a rhythmic pattern of activity that persists close to, but not exactly, a 24-hour cycle (consistent peaks at the same times each day -> shows that its internally regulated)
- Period Length: The period length of the free-running rhythm should remain relatively constant across multiple cycles.
- Phase Shifts: When exposed to external time cues, such as changes in light-dark cycles, the organism’s activity rhythm should be capable of adjusting or “entraining” to these cues by shifting its phase.
Persistence in Constant Conditions: Even when placed in constant environmental conditions (e.g., constant darkness), the organism should maintain its rhythmic activity pattern, demonstrating that its circadian rhythm is not simply a response to external stimuli but is generated internally.
what does left bending in an actogram mean?
occurs when the activity onset or offset times of an organism’s circadian rhythm occur earlier each day compared to the previous day.
This can indicate a circadian rhythm with a period length slightly shorter than 24 hours, often referred to as a “short” period.
what does right bending in actograms mean?
Right bending occurs when the activity onset or offset times of an organism’s circadian rhythm occur later each day compared to the previous day.
This can indicate a circadian rhythm with a period length slightly longer than 24 hours, often referred to as a “long” period.
what does no bending imply on actograms?
No bending occurs when the activity onset or offset times of an organism’s circadian rhythm remain relatively constant over time, without a noticeable trend towards earlier or later times each day.
This can indicate a circadian rhythm with a period length very close to 24 hours, often referred to as a “near-24-hour” period.
(right/left/no):
___ bending suggests that the organism’s internal clock is running slightly faster than the external 24-hour day, causing its activity rhythm to advance each day.
___ bending suggests that the organism’s internal clock is running slightly slower than the external 24-hour day, causing its activity rhythm to delay each day.
___ bending suggests that the organism’s internal clock is closely aligned with the external 24-hour day, with minimal daily drift in activity timing.
left; right; no
what is the circadian rhythm generator?
suprachiasmatic nucleus (SCN)
why is the SCN the circadian rhythm generator?
just above the optic chiasm bc the cue that entrains the clock to 24hr is light0> want to be close to the light transmission pathway
some optic fibers innervate the SCN (a subset of retinal ganglion cells directly innervate the SCN)
what is the step-by-step mechanism of the mammalian circadian clock?
- input pathways
- CLOCK-BMAL1 activation
- Transcription of Per and Cry
- Per/cry complex formation
- nuclear translocation
- inhibition of CLOCK-BMAL1
- degradation of per/cry
(8. additional regulation) - output pathways
what are the input pathways of the circadian clock?
The circadian clock receives input from environmental cues, primarily light-dark cycles, through specialized photoreceptor cells in the retina of the eye.
Light information is transmitted via the retinohypothalamic tract to the SCN, where it synchronizes the internal clock to the external day-night cycle.
what do CLOCK and BMAL1 do?
The primary positive elements of the mammalian circadian clock are two transcription factors, CLOCK (Circadian Locomotor Output Cycles Kaput) and BMAL1 (Brain and Muscle ARNT-like 1).
These proteins form a heterodimeric complex that binds to specific DNA sequences called E-boxes in the promoters of target genes, including Period (Per) and Cryptochrome (Cry) genes.
what are Per and Cry?
The Per and Cry genes are among the primary negative feedback elements in the circadian clock.
After transcription and translation, PER and CRY proteins form heterodimeric complexes and inhibit the activity of the CLOCK-BMAL1 complex.
This inhibitory action suppresses the expression of Per and Cry genes, creating a negative feedback loop.
what is the per/cry nuclear translocation?
The PER/CRY complex undergoes post-translational modifications and translocates into the nucleus.
Once inside the nucleus, it inhibits the transcriptional activity of CLOCK-BMAL1, thus repressing its own expression as well as that of other clock-controlled genes.
what are REV-ERB alpha and ROR alpha?
Another layer of regulation involves the nuclear receptors REV-ERBα (Reverse-erb alpha) and RORα (Retinoic acid receptor-related orphan receptor alpha).
These proteins compete for binding to ROR response elements (ROREs) in the Bmal1 promoter.
REV-ERBα represses Bmal1 transcription, while RORα activates it. This interplay between REV-ERBα and RORα provides additional regulation of the core clock machinery.
what are the output pathways of the circadian clock?
The circadian clock regulates downstream physiological processes and behaviors through output pathways involving clock-controlled genes.
These genes, whose expression is directly or indirectly regulated by the core clock components, mediate the circadian control of diverse cellular processes, including metabolism, hormone secretion, and sleep-wake cycles.
what does the locomotor activity rhythms of mice KO for BMAL1 gene look like?
disruption of bmal1 kills the clock
bmal1 the one and only component essential for the clock
need to take both per or both cry genes to get rid of the clock
(T/F): bmal1 the only one where single KO can disrupt the clock
true!
(T/F): the circadian clock is uninvolved in anticipation.
False!
why is the clock so complicated if light is sufficient to activate it?
photon flux:
- if 100 photons permits a single transcript to get to huge level, decay would be problem
- the clock provides a constant amplitude readout
has evolved bc of the clouds:
- regardless of rain or shine, independent on photon flux of LD cycle, circadian clock produces constatn readouts everyday regardless of how the whether is, rain or shine
what happens when Per protein is phosphorylated in certain sites?
it’s marked for degradation in proteosome pathways
so, per phosphoryalted-> per level drops (role of CKI)
