5. sleep-wake regulatoion & 2-process model

Question 1

sleep initiation is dependent on:

Answer 1

1. sleep homeostasis
2. circadian time
   + metabolic state, immunological state
   + environment: e.g. predation, mating, season, etc.

Question 2

sleep initiation thanks to homeostasis is mediated by different kinds of homeostasis proposed. which ones:

Answer 2

1. synaptic homeostasis
2. firing rate homeostasis
3. ion homeostasis
4. energy homeostasis

Question 3

what is the molecular mechanism of synaptic homeostasis?

Answer 3

mGluR1/5 receptor on dendritic spines signals for LTP, when bound to IP3R with the Homer1a-long variant.
The homer1a-short variant is inhibited by noradrenalin (during wake).

During sleep the homer1a-short is promoted by adenosine and absence of noradrenalin. This causes no connection between mGluR1/5 and IP3R to form -> LTD.

Question 4

what is the mechanism behind the energy homeostasis theory of sleep?

Answer 4

Adenosine theory:
neuronal activity induced energy depletion: ATP -> ADP -> AMP -> Adenosine.
Adenosine is an inhibitory neurotransmitter, that decreases neuronal activity and promotes sleep.

• adenosine is thought to be made in neurons and astrocytes

Question 5

how is sleep homeostasis regulated in drosophilia:

Answer 5

waking to sleep: waking -> R2 increase -> dFB neurons activity increase (thanks to internalized sandman channel and open ShakerKv channel) -> sleep
- dopamine can switch dFB activity to wake

Question 6

what is SIK3:

Answer 6

AMP-activated protein kinase-related kinase
- regulates sleep homeostasis
- mutation in SIK3: NREM increase thanks to decreased PKA recognition