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Title: Neuroscience - Synchronizing behaviour with the environment (circadian rhythms and sleep/wake cycles - Lecture 8
Description: My notes from my module 'Neuroscience' made in my second year at the University of York. They're in the format of the presentation on the left with small powerpoint slides, and the transcript of what was said during that slide on the right.
Description: My notes from my module 'Neuroscience' made in my second year at the University of York. They're in the format of the presentation on the left with small powerpoint slides, and the transcript of what was said during that slide on the right.
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Slislide 1
Module BIO00009I
Neuroscience
Lecture 8
Synchronizing behaviour with the environment
(circadian rhythms and sleep/wake cycles)
Sangeeta Chawla
sangeeta
...
ac
...
Neuronal cell signalling
Intracellular signalling
- GPCR and Ca2+ signalling
- Modulation of synaptic transmission
L6
...
Pharmacology of reward pathways
-The reward pathway
-Synaptic targets of dependence-producing drugs
L8
...
Appreciate the mechanisms by which behaviour is
synchronized to day-night cycles
...
Explain and evaluate how our understanding of behaviour
and neural circuits has been inferred from particular
experiments
...
Synchronizing behaviour with the environment
Introduction
Motivation and Behavior
1
...
Hypothalamic neurons have receptors for the hormone,
leptin (produced by fat tissue) that suppresses appetite and stimulates
metabolic rate
...
Motivational states driven by rewarding/pleasureable and
reinforcing effects of a stimulus
Feeding- We tend to eat much more of “palatable food” than
bland diet or Sexual behavior – a drive towards pleasure fulfillment
Reward pathway and associative learning
3
...
Controlled by the suprachiasmatic nucleus
Slide 5
L8
...
Light can reset the
biological clock/SCN
...
Central pacemaker located in hypothalamus of brain
...
Its an endogenous rhythm set by SCN
The SCN recieves light input from environment,
allowing SCN to modulate the phase at which we
operate
...
Thecentral
pacemaker affects other things such as organs
...
The SCN re-synchronises if
they become out of sync
...
How?
They synchronise by interacting with periheral clocks
via hormones
...
Theres circadian rhythms in autonomous actions such
as:
Body temp- higher in day
...
Circadian rhythm
changes temperature around that set point
...
Take neurons out and cultured them on multi
elecctrode array and monitor AP firing
...
Synchronizing behaviour with the environment
The SCN
Circadian firing rhythms
in SCN neurons
Recording from Individual SCN neuron
(SCN neurons
cultured on a multielectrode array)
Slide 7
L8
...
Almost all cells/metabolic are in circadian rhythm
Pancreas secretes insulin in circadian manner
Lots of enzymes released at night
GI tract- many metabolic functions occur in this
matter
Gastric emptying nighttime- much slower than during
daytime
Don’t learn details! Metabolism is circadian
Slide 8
L8
...
Purves
Slide 9
L8
...
Per and Cry proteins are translated, associate and diffuse back into nucleus
inhibiting Clock/Bmal1 to prevent their own transcription (feedback)
...
Slide 10
L8
...
Trans
feedback causes rhythm
...
Screen mutants and isolate those
who didn’t have rhythm and sequence them to find
out which genes are responsible
...
Feedback inhibition of cry is relieved when per/cry is
phosphorylated
...
This allows the
cycle to start again, whole thing takes 24h
...
A defect in the human homologue of
the period gene was identified as a cause of the sleep
disorder FASPS (Familial advanced sleep phase
syndrome)
When degraded can begin cycle of
transcription/translation again
...
The
mechanism is highly conserved
Took plant, opens/closes leaves in response to light
...
Mutagenesis screen, look for mutant flys
...
Synchronizing behaviour with the environment
Molecular mechanisms
Genetics and the identification of core clock genes
Period::luciferase signal
in isolated wing in DD
Can measure signal in
slices
...
Period2::luciferase
in organotypic slice culture
of the SCN
Per::luciferase- took promoter of this gene and put it
upstream to other gene, it drives the expression of
this new gene in a circadian manner
...
The enzyme
interacts with luciferin, converting ATP light
...
Can combine with other factors- eg in mice look at
body temp (1 degree circadian cycle)
Video saw light up and then disppear
...
If they
were from SCN they would continue for much longer
(can be a year!)
Slide 12
Genetics and the identification
of core clock genes
Wild-type
Per1, Per2
gradual loss of rhythmicity as turn light off
Bmal1
Clock/Npas2 (double knockout)
Complete loss of rhythmicity
Sensory stimulus shows ____
Slide 13
L8
...
Glutamate and neuropeptide PACAP
activate signalling pathways that
Activate transcription factor CREB
CREB binds CRE element in the Per
gene inducing transcription
How does light entrain
the SCN master clock?
Yellow = light on but mice are nocturnal so more quiet
then!
SCN firing/feedback loop is behavioural response
downstream central oscillator/pacemaker and same in
humans
...
They release at the
synapse glutamate
...
Glutamate activates
Ca2+ influx via a receptor, levels increases and cAMP
sometimes
...
Cre etc have DNA binding elements which bind creb
...
Synchronizing behaviour with the environment
Entrainment
How does light entrain
the SCN master clock?
Rods and Cones responsible for visual
transduction via Rhodopsins
RGCs responsible or nonvisual light
input to SCN via melanopsin (pigments)
Slide 15
L8
...
These are blots and cones, their
activation is responsible for sight, they project onto
your visual coretx via the palates
...
Visual/non visual inputs have different effects
observed people who are visually blind still have
rhythm but light input occurs by v ganglian cellsoperating by
Trans feedback!
During day SCN makes mRNA translated to proteins,
which diffuse back into nucleus and repress their own
transcription
...
Light can
change this, provide light in night and SCNs will fire
...
Synchronizing behaviour with the environment
Sleep/wake circuits
Arousal systems
Morphine inhibits LC neurons
Cocaine activates LC and Raphe nuclei
Arousal systems:
1
...
Raphe nuclei (serotonerigic)
3
...
Tuberomammillary nucleus of hypothalamus (histaminergic)
Sleep controlled by different anatomical regions in
brain
...
Cholingeric- release acetylcholine onto the cortex and
callosum
...
During sleep brain changes firing pattern, mediates via
decrease in activity and increase in sleep center
...
Cocaine- causes insomnia, because they actiavte
neurones in LC and raphe nuclei due to their effects
on transporter systems
...
Histamines- antihistamines block downstream
histamine receptors of synamergic signalling causing
drowsiness
...
Slide 17
L8
...
The SCN inhibits VLPO neurons indirectly via
the subparaventricular zone (SPZ) and
the dorsomedial nucleus of the hypothalamus (DMH)
(SCN is active in light VLPO active in sleep)
Sleep- actively induced phenomenon, neurones have
to be switched off, take cows which are awake and
stimulate VLPO and they fall asleep- sleep is active!
Have receptors for adenosine, for when brain uses lots
of E you release adenosine which collects and
activates the VLPO
...
Caffine acts on the adneosine receptors and blocks
them, means the normal adenosine cant act on its
receptors
...
If you’ve flown from
UK to eastern destination, and its morning there but
night in uk, the light, the SCN activated, inhibiting
VLPO stopping you from sleeping
...
Synchronizing behaviour with the environment
Summary
4
...
-The Suprachiasmatic nucleus (SCN) Master clock is entrained by light
- Transcription-translation feedback loop (TTFL) as cellular basis of
timekeeping
- The SCN inhibits sleep-promoting neurons
5
...
-
Slide 19
Disruption of TTFL clock genes disrupts behavioral circadian rhythms
Cellular rhythms can be assessed using Per2::Luciferase
Title: Neuroscience - Synchronizing behaviour with the environment (circadian rhythms and sleep/wake cycles - Lecture 8
Description: My notes from my module 'Neuroscience' made in my second year at the University of York. They're in the format of the presentation on the left with small powerpoint slides, and the transcript of what was said during that slide on the right.
Description: My notes from my module 'Neuroscience' made in my second year at the University of York. They're in the format of the presentation on the left with small powerpoint slides, and the transcript of what was said during that slide on the right.