Special Biochemistry Seminar
Circadian rhythms are periodic changes in animal behaviour and physiology, synchronized with planetary rhythms. These rhythms are regulated by the circadian clock, a transcription/translation negative feedback loop that regulates the rhythmic expression of several hundred genes in a 24-hour period. Mutations in genes that make up the circadian clock can lengthen, shorten, or eliminate circadian rhythms, observable using locomotor behaviour in Drosophila. We have shown that targeted mutations that block a specific regulatory mechanism within the circadian clock indeed alter locomotor behaviour, but strikingly affect individual neuronal clocks differently, ranging from complete disruption to no effect. Thus, we hypothesise that a single mutation can disrupt the phase or period of distinct circadian clocks in different regions of the brain differently, causing desynchrony between individual clocks. We also suggest that this desynchrony may underlie some behavioural disorders. In order to test our hypothesis, we created a method to measure transcription oscillations in different neurons in vivo, in real time. We have shown that disruption of a key neurotransmitter, thought to govern downstream circadian clocks, affects them differently. Preliminary data also suggest that altering some clocks influence only a subset of downstream clocks within the neuronal network, suggesting a more flexible neuronal hierarchy than previously assumed. We propose that understanding the molecular etiology of circadian behaviour will require determining the mechanism underlying clock regulation in each neuronal cluster as well as the neuronal combinations that converge to regulate specific behaviours.
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