Lecture 11 Rhythms in the brain and sleep

Question 1

how can you define sleep?

Answer 1

behaviourally as a normal absence of consciousness

electrophysiologically as pattern of specific brain wave activity

Question 2

transition between sleep/wakefullness?

Answer 2

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

Question 3

why do we sleep?

Answer 3

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

Question 4

sleep changes with age?

Answer 4

high when young, less over lifetime.

Question 5

organism size and sleep bout duration?

Answer 5

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.

Question 6

how do we measure sleep?

Answer 6

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.

Question 7

EEG components

Answer 7

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.

Question 8

slow wave sleep?

Answer 8

stages 2/3/4

non REM sleep

Question 9

REM sleep?

Answer 9

paradoxical sleep.
looks closer to being awake.

dreamy dreams

Question 10

first hour of sleep

Answer 10

Kleitman 1953

specific progression of sleep stages occur.
~15 minutes in each stage
followed by rapid transition into REM sleep.

Question 11

progression of sleep throughout the night

Answer 11

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.

Question 12

how do you measure REM sleep?

Answer 12

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.

Question 13

what controls sleep?

Answer 13

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

Question 14

Cervaeu Isole

Answer 14

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

Question 15

Encephale Isole

Answer 15

Frederic Bremer, 1935

Transection between the medulla and spinal cord, brain displays all sleep stages, so spinal input is uneccessary for waking.

Question 16

what led to ARAS?

ascending reticular activating system

Answer 16

since forebrain can only produce SWS, brainstem must prod REM and turn off SWS.

Question 17

flip flop model?

Answer 17

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)

Question 18

Adenosine

Answer 18

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

Question 19

ARAS pathways?

Answer 19

Dorsal pathway:
Thalamus, cerebral cortex

Ventral pathway:
basal forebrain

Question 20

neuro control of arousal/wakefulness

Answer 20

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).>??

Question 21

what does EEG measure/Thalamocortical Interactions

Answer 21

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.

Question 22

Thalamic SWS Circuit neural components

Answer 22

Three main types of neuron are involved in interactions between the cortex and thalamus during SWS:

1. Cortical neurons project to thalamus
   (corticothalamic; CT)
2. Thalamic neurons project to cortex
   (thalamocortical; TC)
3. 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.

Question 23

TC cells during SWS

Answer 23

recordings of TC during SWS of cell membrane show hyper polarisation and delpolarisation in a rhythmic fashion, hyper causes brief burst of action potentials.

Question 24

ARAS for SWS

Answer 24

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.

Question 25

brainstem and ARAS pathway

Answer 25

switch off the RE cells and stimulate TC cells promoting asynchronous tonic TC cell firing.

all goes apeshit and they desynchronise EEG.

Question 26

what happens when we sleep then?

Answer 26

Brain isn’t completely switched off during sleep but instead thalamocortical neurons revert to their ‘default’ mode

Question 27

REM sleep characteristics

Answer 27

desync EEG.
muscle paralysis, prevents dreams acting out.
rapid eye movements.

PGO waves:
activity spreads from
Pons –> Geniculate –> Occipital.

Question 28

origins of REM sleep?

Answer 28

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.

Question 29

Neural control of REM features.

Answer 29

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

Question 30

what controls REM generating cells?

Answer 30

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 .

Question 31

reciprocal interaction model

Answer 31

paper online, current theories.