Lecture 8 - Synchronising behaviour with the environment Flashcards
Through what mechanisms is behaviour synchronised to day-night cycles?
- superchiasmic nucleus (SCN) master clock (entrained by light)
- Transcription-translation feedback loop (TTFL) as a cellular basis of timekeeping
- inhibition of sleep promoting neurons by the SCN
What are the three mechanisms involved in motivation and behaviour?
1-Drive states directed towards maintaining physiological homeostasis
-Feeding behaviour/Appetite: controlled patly by the hypothalamus, hypothalamic neurons have receptors for the hormone leptin (produced by fat tissue) that supresses appetite and stimulates metabolic rate
2-Motivational states driven by rewarding/pleasurable and reinforcing effects of a stimulus
-Feeding: tend to eat more ‘palatable food’ than bland diet
-Sexual behaviour - drive towards pleasure fulfilment
-involves the reward pathway and associative learning
3-Anticipatory mechanisms: intrinsic circadian clock driven mecanisms that can turn physiological behavioural responses on/off before tissue need
-controlled by the superchiasmatic nucleus
What are anticipatory mechanisms?
intrinsic circadian clock driven mechanisms which can turn physiological behavioural responses on/off before tissue need
-mostly controlled by the superchiasmic nucleus
Where is the superchiasic clock located?
in the hypothalamus
-acts as a central pacemaker ‘master clock’
How does the SCN synchronise physiological processes with the day-night cycle?
photo-entrainment
-light (a zeitgeber) can reset the biological clock
What processes does the SCN control?
-endocrine system and peripheral nervous system
-rest-activity cycles
-feeding time
-body temperature
-Peripheral clocks:
All organs in the body have a clock that operates at different phases of the SCN
e.g. metabolism is controlled in a circadian manner
heat beat is slow at night
How can it be shown that SCN neurons have a circadian firing rhythm?
culture neurons on a multielectrode assay
record from individual SCN neurons
-show that the firing frequency changes and maintains a circadian rhymth
What organs contain peripheral clocks in circadian metabolism?
Liver - hepatic enzymes show circadian changes
Pancreas - pancreatic enzymes increase their output at night
GI tract - gastric emptying slower after evening meal
What are the features of sleep/wake cycles and how were these shown experimentally?
-sleep occurs with circadian periodicity
-persists under constant condidtions
Experimentally
-the sleep/wake cycles of a volunteer were manipulated
-put in a disued WWII bunker (no external light cues) and given cues that allowed them to calculate the time of day, e.g. radio, eating times,
-showed that with cues, the volunteer fell asleep and awake at roughly the same times
-without cues, although it takes time to adjust, showed a natural circadian rhythm of around 24 hours (26), which persists under constant conditions
CONC - happens by a endogenous mechanisms
What is the molecular mechanisms of maintaining circadian rhythms?
A transcription/translation feedback loop
How were the molecular mechanism of circadian rhythms identified?
- chemical mutagenesis of drosophila
- isolate drosophila arthymic mutants/short/long period mutants through constant darkness actograms (after 12:12 LD cycles)
- sequenced their genome
- identified the Period gene
- circadian rhythms are highly conserved between fly and humans
What is the transcription-translation feedback loop?
- TFs Clock/Bmal1 act as a heterodimer to induce transcription of Per and Cry genes via E-box elements
- Per and Cry proteins are translated, associated and diffuse back into the nucleus
- this inhibits Clock/Bmal1 to prevent their own transcription (feedback)
- during the night Per and Cry proteins are degraded, allowing Clock/Bmal1 to transcribe again
How have plant behavioural experiemtns shed light on the mechanisms of circadian rhythms?
- took plant that responded to light by opening and closing leaves
- put under constant darkness and filmed with an infrared camera
- plant continued to open flowers in circadian rhythm
How did the per::luciferase reporter gene conjugation show Drosophila circadian rhythms after the identification of the Per gene?
- took promoter of the period gene and put upstream of the luciferase gene to drive the expression of that gene in a circadian manner
- luciferase is an enxyme from fire flies which converts luciferase using ATP to light
- can measure circadian rhythm in isolated organs visually
What was experimentally identified about the activity of SCN in mice?
Luciferase::period gene conjugation
3 homologs of the fly period gene - 1,2,3
2 showed the most robustness of circadian rhythms (drosophila have 2 homologs in mammals)
-the light output from the luciferase gene most highly correlated to the circadian rhythm
-however when combined with other paramenters e.g. temp, the light output vaires aound the circadian cycle
Mutageneis of the period genes
-WT showed maintainance of circadian rhythms after loss of light cues
-Per1, Per2 showed gradual loss of circadian rhythms after loss of light cues
-Bam1 and Clock/Npas2 (double knockout) showed complete loss of rhythmicity after loss of light cues
