Lecture 9 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/wakefulness wrt neuronal activity?

Answer 2

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

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 –> rats died 2-3 weeks

Question 4

sleep changes with age

Answer 4

high when young, less over lifetime, chronotype starts advancing at ~0yrs

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- different cognitive states are associated with distinct EEG waveforms.

provides a continuous recording of brain activity.
cheap
non invasive

Question 7

EEG components

Answer 7

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.

Question 8

slow wave sleep in which sleep stages?

Answer 8

stages 2/3/4

non REM sleep

Question 9

REM sleep

Answer 9

paradoxical sleep.

looks closer to being awake.; dreams

Question 10

first hour of sleep

Answer 10

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 to waking levels.

Question 13

Which 3 neural systems control 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.

Question 14

Cervaeu Isole

Which brain area? Sleep onset? NT? Stimulation/ lesion? Inhibited by?

Answer 14

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

Question 15

Encephale Isole

Answer 15

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

Question 16

what led to ARAS?

ascending reticular activating system

Answer 16

since forebrain can only produce SWS, brainstem role REM and turning off SWS.

Question 17

flip flop model?

Answer 17

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)

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

Neural control of arousal/wakefulness- NAd

Answer 20

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

Question 21

Thalamocortical Interactions

Answer 21

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.

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) (Glu)
2. Thalamic neurons project to cortex
   (thalamocortical; TC) (Glu)
3. Thalamic reticular
   neurons (RE) project onto TC (GABA)

Question 23

TC cells during SWS

Answer 23

rhythmic bursting dduring SWS

(recordings of TC during SWS of cell membrane show rhythmic hyper-and-depolarisation, former causes brief burst of action potentials)

Question 24

Thalamocortical intrinsic oscillations

Answer 24

Rhythmic oscillations in different TC cells are asynchronous following TTX block (membranous oscillations retained but Na+ spikes lost)

Question 25

Does the brain switch off during sleep?

Answer 25

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

Question 26

REM sleep characteristics

Answer 26

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.

Question 27

Neural origins of REM sleep?

Answer 27

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 28

Neural control of REM features.

Answer 28

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 29

what controls REM generating cells?

Answer 29

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 30

Neural control of arousal and wakefulness- ACh

Answer 30

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]

Question 31

Neural control of arousal and wakefulness- 5-HTP

Answer 31

Raphe nuclei–> Neocortex, Hippocampus
Thalamus, Basal ganglia Hypothalamus
(+) wakefulness

Question 32

Neural control of arousal and wakefulness- HA

Answer 32

Tuberomammillary nuc. –>
Neocortex, Hippocampus,
Thalamus, Basal ganglia, Hypothalamus

(+) wake (antiHA crossing BBB –> drowsiness)

Question 33

Stage 4 sleep wrt. thalamocortical interactions

Answer 33

Synchronous activity of many thalamic/cortical neurons (results in the delta wave)

Question 34

Awake wrt. thalamocortical interactions

Answer 34

Asynchronous activity across the thalamus/cortex (results in aplha and beta activity)

Question 35

Significance of thalamic reticular neurons (RE) wrt. thalamic SWS circuit

Answer 35

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 36

Brainstem (ACh) inputs to TC (+) and RE (-)…

Answer 36

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

Question 37

Reciprocal interaction model

Answer 37

A complex circuit of excitatory and inhibitory brainstem neurons controls transitions between REM and slow wave sleep (DIAGRAM)

Question 38

Synapses in the thalamocortical sleep circuit

Answer 38

CT and TC are reciprocally excitatory, both send excitatory inputs to RE but RE sends inhibitory input to TC ONLY
(e= Glu, i- GABA)