Lecture 11 Rhythms in the brain and sleep Flashcards
how can you define sleep?
behaviourally as a normal absence of consciousness
electrophysiologically as pattern of specific brain wave activity
transition between sleep/wakefullness?
overall decrease in neuronal activity, but not neccessarily shuttnig down all the brain.
some areas increase in activity, it is a series of precisely controlled brain states.
Sequence determined by activity of specific brain nuclei
why do we sleep?
Sleep is a basic homeostatic need:
Requirement for sleep increases with time awake
Sleep/sleep-like behaviour occurs in all multicell organisms
obviously important therefore.
formation of memories
sleep deprivation is required for maintenance of normal cognitive function.
rats died 2-3 weeks
sleep changes with age?
high when young, less over lifetime.
organism size and sleep bout duration?
sleep bout duration increases with organism size.
smaller organisms have a reduced capacity for wakefulness, alternate short bouts of sleeping/waking.
maybe for increased vigilance.
metabolic burden could be too high on brain.
how do we measure sleep?
electroencephalogram EEG
provides a continuous recording of brain activity.
cheap
non invasive
different cognitive states are associated with distinct EEG waveforms.
can differentiate between asleep, closed eyes etc.
EEG components
alpha activity - fast, large, eyes closed, relaxed
beta activity - being alert, attentive, thinking
stage 1 sleep, theta activity - larger and slower compared to awake.
stage 2 have sleep spindle + K complex, become more and more frequent until in stage 3/4 where continuous high amplitude delta wave activity.
slow wave sleep?
stages 2/3/4
non REM sleep
REM sleep?
paradoxical sleep.
looks closer to being awake.
dreamy dreams
first hour of sleep
Kleitman 1953
specific progression of sleep stages occur.
~15 minutes in each stage
followed by rapid transition into REM sleep.
progression of sleep throughout the night
5 sleep cycles on average per night.
REM duration increases/SWS decreases throughout sleep bout.
deep sleep (stage 4) present in only the first 2 cycles.
how do you measure REM sleep?
eye movement with EOG (electroculogram) mainly occurs during REM.
muscle movements in the neck EMG (electromyogram) prominent at waking and REM transitions.
heart rate/respiration peak during REM compared to waking levels.
what controls sleep?
Forebrain system that can independently support SWS.
Brainstem system that activates the forebrain into waking.
System in the pons that triggers REM sleep.
Frederic Bremer 1935
Cervaeu Isole
Bremer
cut off brainstem, only forebrain.
constant SWS, therefore forebrain can produce SWS.
SWS initiation - particularly VLPO (ventraolateral preoptic area).
VLPO neurons become active at sleep onset.
are inhibitory/GABA project widely throughout brain.
VLPO stimulation induces SWS, lesion abolishes it.
VLPO neurons are inhibited by neurochemicals associated with arousal, NA, ACh, 5HT
Encephale Isole
Frederic Bremer, 1935
Transection between the medulla and spinal cord, brain displays all sleep stages, so spinal input is uneccessary for waking.
what led to ARAS?
ascending reticular activating system
since forebrain can only produce SWS, brainstem must prod REM and turn off SWS.
flip flop model?
Saper 2005
sleep promoting neurons in VLPO oppose wake promoting neurons in the brainstem.
mutually inhibitory.
ie DR - serotonin,
LC/locus coeruleus -NA
TMN - GABA
wake promoting neurons excited by Orexin.
Sleep promoting neurons excited by Adenosine (probably)
Adenosine
Adenosine levels increase during intense neural activity
adenosine levels increase during waking and decrease during sleep
adenosine agonists increase sleep
adenosine receptor antagonists (e.g., caffeine) inhibit sleep
adenosine activates VLPO (sleep promoting) neurons
ARAS pathways?
Dorsal pathway:
Thalamus, cerebral cortex
Ventral pathway:
basal forebrain
neuro control of arousal/wakefulness
Noradrenaline:
LC recordings in rat of NA.
declines leading to sleep,
almost no firing during REM, big rise when wake
Serotonin:
Histamine:
antihistamines with no ability to cross BBB lack this property.
Acetylcholine:
Ach cells in brainstem project to the thalamus, cortex, basal ganglia, and basal forebrain.
Stimulating cholinergic neurons in the ascending reticular activating system produces arousal.
if stimulate Ach neurons in cat which was asleep, woken up with stimulation.
show high firing during wake and REM sleep, low in SMS.
EEG shifts from sync (high amp/low freq) to desync (opposite).>??
what does EEG measure/Thalamocortical Interactions
sum of activity of lots of cells under electrodes.
high amp/low freq means groups of cells becoming hyper-polarised and de-polarised in cortex in a rhythmic fashion.
cortex driven from inputs in thalamus, therefore rhythmic thalamus inputs.
Thalamocortical cells receive brainstem inputs from locus coeruleus (NA), raphe nuclei (serotonin) and pontine nuclei (cholinergic). dorsal?
brainstem activity decreases:
thalamic rhytmic burstin and the related synchrony of cortical targets.
results in the lower amp asynchronous activity recorded.
Thalamic SWS Circuit neural components
Three main types of neuron are involved in interactions between the cortex and thalamus during SWS:
- Cortical neurons project to thalamus
(corticothalamic; CT) - Thalamic neurons project to cortex
(thalamocortical; TC) - Thalamic reticular
neurons (RE) project onto TC
RE also recieve excitatory input from CT and TC cells.
1/2 both excitatory Glut
3 inhibitory GABA
RE cells have dendro dendritic synapses with other RE cells which allow them to synchronise rhythmic firing in TC cells throughout periods of inhibition.
TC cells during SWS
recordings of TC during SWS of cell membrane show hyper polarisation and delpolarisation in a rhythmic fashion, hyper causes brief burst of action potentials.
ARAS for SWS
doesnt actually rely on CT and RE circuit.
know this because:
block AP with TTX tetrodoxin (blocks Na channels).
isolates cell from the rest of circuit, still shows the oscillations, it is intrinsic.
the circuit is important for synchrisity. they are out of sync without.
RE cells have dendro dendritic synapses with other RE cells which allow them to synchronise rhythmic firing in TC cells throughout periods of inhibition.
brainstem and ARAS pathway
switch off the RE cells and stimulate TC cells promoting asynchronous tonic TC cell firing.
all goes apeshit and they desynchronise EEG.
what happens when we sleep then?
Brain isn’t completely switched off during sleep but instead thalamocortical neurons revert to their ‘default’ mode
REM sleep characteristics
desync EEG.
muscle paralysis, prevents dreams acting out.
rapid eye movements.
PGO waves:
activity spreads from
Pons –> Geniculate –> Occipital.
origins of REM sleep?
cholinergic cells in the pons.
PPT/LDT (peribrachial area)
can fire at a high rate during REM and waking.
some only REM (REM-ON cells)
firing increases just before REM onset.
Neural control of REM features.
Projections of the cholinergic cells of the peribrachial area drive all the characteristic features of REM sleep.
muscle paralysis via medulla
rapid eye movements via tectum
EEG desync cortex
what controls REM generating cells?
5HT and NA inputs to the peribrachial area appear to suppress REM sleep.
Raphe and LC switch off during SWS
Decreased 5HT and NA input allows peribrachium to become active and REM to start .
reciprocal interaction model
paper online, current theories.
