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
How does light entrain the SCN master clock?
- Melanopsin-containing photosensitive retinal ganglion cells (RGC) in the vertebrate eye sense light signal and the axons synapse onto the SCN neurons via the retinohypothalamic tract, releasing glutamate and PACAP
- Glutatmate and neuropeptide PACAP (interacts with GPCR to increase cAMP levels) activate signalling pathways that activate the CREB TF.
- CREB binds the CRE element in the Per gene inducing transcription (and can reset the clock)
What structures in the eye are reponsible for visual transduction?
Rods and Cones via rhodopsin
Are RGCs responsible for visual or nonvisual light input?
nonvisual light input to the SCN via melanopsin
How does the SCN control sleep/wake cycles?
communication with neural circuits that control arousal and sleep
-during day mRNA for Cry and Per is made
-mRNA is translated into proteins which are transported to the nucleus and repress transcription
this has an opposite effect in mice and men
What are the structures involved in arousal systems?
Pons
-locus coeruleus (noradrenergic )
-raphe nuclei (serotonergic)
-Reticular activating system PPT, LDT (cholinergic)
Tubermammilary nucleus of the hypothalamus (histaminergic - histones maintain arousal state)
release neurotransmitter onto the thalamus and cortex
What are the activites of morphine and cocaine on arousal systems?
Morphine inhibits LC neurons (leads to drowiness, acts on opiate receptors via a G protein coupled receptor mechanism)
Cocaine acitvated LC and raphe nuclei
How are arousal systems involved in obtaining sleep?
Requires the switching off of arousal systems by neuronal activity of sleep centres
When are the SCN and VLPO active and how to they interact?
SNC active in light
-inhibits VLPO neurons indirectly via the subparaventricular zone and the dorsomedial nucleus of the hypothalamus
VLPO active in sleep
-Ventrolateral peroptic VLPO area in the hypothalamus stimulates sleep (GABAergic) by inhibiting the arousal centres
