Regulation of Sleep and Wakefulness

Sleep and wakefulness are regulated by a number of neurotransmitters, as well as neuromodulators within specific brain regions1.

Physiology

The underlying physiology of sleep and wakefulness is complex. Different Neurons and Neurotransmitters promote different states of sleep and wakefulness. They are therefore categorised based on state-specific discharge patterns and/or transmitter release and other neurobiological classifications.

State-Specific Discharge Patterns:

Neurons are classifiable based on their discharge-pattern. During each behavioral state, there are neurons that fire at a higher rate as others. More specifically:

• Wake-On (/Rem-Off)
• Wake-On/ Rem-On
• Rem-On
• NRem-On

State-Specific Transmitter Secretion

In neurobiology, neurons are also classified by their state-specific transmitter release.

Monoamines (here: serotonin, norepinephrine, histamine): Densest release during wakefulness.

Acetylcholine: Densest release during both wakefulness and Rem-sleep

GABA ( γ-aminobutyric acid): Densest release during NREM-sleep.

Summarizing Neurotransmitters regulating the Behavioral States:

Wakefulness

Acetylcholine, Serotonin, Norepinephrine, Histamine, Dopamine, Orexins, Glutamate (,GABA)

NREM

GABA, Adenosine

REM

Acetylcholine, GABA

The neurotransmitter GABA has brain region specific effects on behavioral states.

GABA in the pontine reticular formation promotes sleep and decreases sleep, by inhibiting the secretion of acetylcholine, which promotes Rem-sleep.

However, neurons activated by GABA in the basal forebrain fire the fastest during NRem-sleep, and is NRem promoting.

Adenosine, the other major neurotransmitter involved in the onset of NRem-sleep, increases proportional to the time spent awake in the basal forebrain. It is the neurotransmitter thouoght to be the major regulator of Process S in the 2-Process Model of Sleep.