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Wakefulness
Segment
1
Learning Points
Learning Point
States of sleep and wakefulness are
generated by complex interactions
between many neurotransmitters
and neuromodulators acting at
multiple sites within the brain
PFC (Glu)
BF (ACh, GABA)
LH (Hcrt/Ox)
Thalamus
(ACh,Glu)
LDT/PPT (ACh)
DR (5-HT)
VLPO (GABA)
LC (NE)
TMN (HA)
PRF
VTA/SN (DA)
(Glu, GABA)
Thalamus
LDT/PPT
PFC (Glu)
(ACh,Glu)
(ACh)
DR (5-HT)
LC (NE)
BF (ACh,
GABA)
VLPO
(GABA)
LH (Hcrt/Ox)
PRF
TMN (HA)
VTA/SN (DA)
(Glu, GABA)
Learning Point
Sleep neurobiology phenotypes
neurons based on chemical
identity, discharge patterns,
projection pathways, transmitter
release, and receptors expressed
Learning Point
Neurochemical identity, discharge
patterns, and transmitter release
patterns are some of the lower level
phenotypes generating the higher
level phenotypes of sleep and
wakefulness
Spikes/sec
Spikes/sec
Wake-On/REM-O
Wake-On/REM-On
Spikes/sec
Spikes/sec
NREM-On
Spikes/sec
Spikes/sec
Wake-On/REM-O
Wake-On/REM-On
Spikes/sec
Spikes/sec
NREM-On
Spikes/sec
Spikes/sec
Wake-On/REM-O
Wake-On/REM-On
Spikes/sec
Spikes/sec
NREM-On
Spikes/sec
Spikes/sec
Wake-On/REM-O
Wake-On/REM-On
Spikes/sec
Spikes/sec
NREM-On
Baghdoyan & Lydic, in Basic Neurochemistry ed: Brady et al., Elsevier, 2012, p. 985
NREM Sleep
REM Sleep
Acetylcholine
GABA
Acetylcholine
Serotonin
Norepinephrine
Histamine
Adenosine
Dopamine
HypocreFn/Orexin
Glutamate
Glutamate (?)
Clinical Relevance
New medications developed to enhance
sleep or wakefulness will be most
effective if they act on multiple
transmitter systems
Medications used to treat other medical
conditions negatively impact sleep
Learning Points
Interactions between transmitters determine
behavioral state at any moment in time
The same transmitter may have opposite
effects on sleep and wakefulness depending
on site of action within the brain
For example