Lecture 9 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/wakefulness wrt neuronal activity?
overall decrease in neuronal activity, but not global
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 –> rats died 2-3 weeks
sleep changes with age
high when young, less over lifetime, chronotype starts advancing at ~0yrs
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- different cognitive states are associated with distinct EEG waveforms.
provides a continuous recording of brain activity.
cheap
non invasive
EEG components
beta activity - being alert, attentive, thinking
alpha activity - fast, large, eyes closed, relaxed
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 –> continuous high amplitude delta wave activity.
slow wave sleep in which sleep stages?
stages 2/3/4
non REM sleep
REM sleep
paradoxical sleep.
looks closer to being awake.; dreams
first hour of sleep
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 to waking levels.
Which 3 neural systems control sleep?
Forebrain system that can independently support SWS.
Brainstem system that activates the forebrain into waking.
System in the pons that triggers REM sleep.
Cervaeu Isole
Which brain area? Sleep onset? NT? Stimulation/ lesion? Inhibited by?
cut off brainstem, only forebrain –> constant SWS –> forebrain can produce SWS.
SWS initiation - particularly VLPO (ventraolateral preoptic area).
VLPO neurons become active at sleep onset; 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
Transection between the medulla and spinal cord–> brain displays all sleep stages, so spinal input is unnecessary for waking.
what led to ARAS?
ascending reticular activating system
since forebrain can only produce SWS, brainstem role REM and turning off SWS.
flip flop model?
Sleep promoting neurons in VLPO oppose wake promoting neurons in the brainstem and hypothalamus
–> mutually inhibitory.
DR - 5-HTP
LC/locus coeruleus -NAd
TMN (Hyp)- GABA/HA
LDT/PPT- ACh
(conceptual as these connections are not direct)
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
Neural control of arousal/wakefulness- NAd
Locus Coeruleus–>
Neocortex, Hippocampus, Thalamus, Hypothalamus, Cerebellum, Brainstem
LC recordings in rat of NA.
declines leading to sleep,
almost no firing during REM, big rise on waking
Thalamocortical Interactions
Changes in mental states revealed by EEG result from changes in communication between thalamus and cortex
Thalamocortical cells receive brainstem inputs from locus coeruleus (NA), raphe nuclei (serotonin) and pontine nuclei (cholinergic)
Activity in brainstem afferents decreases:
thalamic rhythmic bursting 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) (Glu) - Thalamic neurons project to cortex
(thalamocortical; TC) (Glu) - Thalamic reticular
neurons (RE) project onto TC (GABA)
TC cells during SWS
rhythmic bursting dduring SWS
(recordings of TC during SWS of cell membrane show rhythmic hyper-and-depolarisation, former causes brief burst of action potentials)
Thalamocortical intrinsic oscillations
Rhythmic oscillations in different TC cells are asynchronous following TTX block (membranous oscillations retained but Na+ spikes lost)
Does the brain switch off during sleep?
Brain isn’t completely switched off during sleep but instead thalamocortical neurons revert to their ‘default’ mode
REM sleep characteristics
desync EEG (more like waking)
muscle paralysis, (prevents dreams being acted out);
rapid eye movements.
Onset characterised by PGO waves:
activity spreads from
Pons –> Geniculate –> Occipital.
Neural 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 .
Neural control of arousal and wakefulness- ACh
Ach cells in brainstem –> thalamus, cortex, basal ganglia, and basal forebrain.
Stimulating Ach neurons in ascending reticular activating system produces arousal (wakes sleeping cat)
Show high firing during wake and REM sleep, low in SMS.
EEG shifts from sync (high amp/low freq) [SWS] to desync (low amp/ high freq) [REM/waking]
Neural control of arousal and wakefulness- 5-HTP
Raphe nuclei–> Neocortex, Hippocampus
Thalamus, Basal ganglia Hypothalamus
(+) wakefulness
Neural control of arousal and wakefulness- HA
Tuberomammillary nuc. –>
Neocortex, Hippocampus,
Thalamus, Basal ganglia, Hypothalamus
(+) wake (antiHA crossing BBB –> drowsiness)
Stage 4 sleep wrt. thalamocortical interactions
Synchronous activity of many thalamic/cortical neurons (results in the delta wave)
Awake wrt. thalamocortical interactions
Asynchronous activity across the thalamus/cortex (results in aplha and beta activity)
Significance of thalamic reticular neurons (RE) wrt. thalamic SWS circuit
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 (ACh) inputs to TC (+) and RE (-)…
…switch off the RE cells and stimulate TC cells promoting asynchronous tonic TC cell firing
Reciprocal interaction model
A complex circuit of excitatory and inhibitory brainstem neurons controls transitions between REM and slow wave sleep (DIAGRAM)
Synapses in the thalamocortical sleep circuit
CT and TC are reciprocally excitatory, both send excitatory inputs to RE but RE sends inhibitory input to TC ONLY
(e= Glu, i- GABA)
