L11 - Sleep Neuroanatomy and Neuropharmacology Flashcards
Describe the wakefulness system
2 groups of neurons that use…:
- Ach - when stimulated, makes cortex more active. projects to the thalamus (relay centre for the brain and allows for wakefulness of whole brain), and projects to hypothalamus and basal forebrain, which again projects to all the cortex
- monoamines - they primarily stimulate cortex via hypothalamus, basal forebrain loop and some of the thalamic loop.
maintained by numerous cell groups projecting to thalamus, hypothamalus, basal forebrain and cortex.
Orexin cells in lateral hypothalamus have a general excitatory influence over this system and act as master controllers in wakefulness.
Describe the Noradrenergic patways in wakefullness.
NA cells scattered throughout the brainstem and particularly locus coeruleus.
Projects to virtually all of the brain, specifically thalamus and hypothalamus.
Drugs that promote NA activity increases wakefulness (amphetamine) and drugs that inhibit it decrease wakefulness.
cells in LC are more active during wakefulness than in sleep.
LC cells also have lower activity relative to other neurons in sleep.
What are orexin/hypocretin neurons?
They are “master controllers” tells the other groups of neurons when to become active.
Cells are in the lateral hypothalamus, and orexin is the NT.
neurons are active during wake, and have excitatory projections to RMN, Raphe, LC, PPT and LDT and BF, and the cortex directly to maintain wakefulness.
What is the VLPO?
Ventrolateral pre-optic nucleus - neurons in the anterior hypothalamus that inhibit all nuclei in the wakefulness system, usuch as orexinergic neurons.
It uses GABA and GALANIN (inhibitory NTs).
found in TMN, LC and raphe.
the inhibition is bi directional, so allows stable states. only one is active at a time. (Sleep or wakefulness)
mastercontroller for sleep!!
what is VLPO activity like during sleep?
- elevated activity during sleep, but not during sleep deprivation.
- not a marker of how sleepy we’re feeling, simply causes sleep.
- 2 regions:
VLPO cluster (NREM) and Extended VLPO (REM)
when both were lesioned, only lost 50% of sleep
What does the basal forebrain do when stimulated?
in cats, when stimulated whilst day dreaming, they sleep.
when stimulated when active, they lose interested.
does this cause sleep?
when lesioned, it didnt destruct sleep. possibly due to VLPO acitvity. maybe VLPO TAKES OVER.
How is the sleep and wakefulness system so stable and consolidated into blocks??? with so many different inputs!?
FLIP-FLOP SWITCH
it switches either on or off. can’t be in the middle!!
As homeostatic sleep drive and circadian rhythm signal go up, it pushes VLPO action up, inhibits orexin and TMN, LC - Raphe, and induces sleep.
as circadian alerting signal increases, it pushes TMN, LC Raphe to increase, orexin increas and VLPO inhibited, iinducing WAKEFULNESS.
What are the REM sleep-on neurones?
A flip-flop switch controls whether we go into nrem or REM sleep…
GABAergic neurons in the sublateral dorsal region of pons are highly active in REM and inhibit REM-off neurons.
Cholinergic cells located in the LDT/PPT act as the finger on the switch for the cells, and switch on rem! they also project to the spinal cord to inhibit any movement - paralysis
theyre very active during REM sleep, moderately during wakefulness and inactive in nrem.
What are the REM sleep-off neurones?
Ventrolateral periaqueductal grey / lateral pontine tegmentum GABAergic neurons inhibits REM!
These cells are inactive during REm and active during non rem. they appear to inhibit SLD and REM sleep when active.
activated by LC and Raphe (Finger on switch) as well as extended by the VLPO neurons.
Role of orexin in sleep?
- stimulates the arousal systems and inhibits VLPO
- associated stimulation of LC and Raphe inhibits REM
THUS low levels of activity in the orexin system ALLOWS for REM sleep to occur
if low levels of orexin occured during wakefulness it would make it difficult to maintain awake, allow the intrustion of REM ….. NARCOLEPSTY!!
Describe the Flip Flop switch for REM!!
low orexin –> low LC and Raphe activity –> allows for PPT and LDT acitivity –> inhibits vlPAG and LPT…….
need to draw this out :(
