REM Sleep Origin in the Brain
REM sleep originates primarily in the pons (brainstem), specifically in the sublaterodorsal nucleus and precoeruleus region, which contain glutamatergic "REM-on" neurons that generate and maintain REM sleep. 1
Primary Anatomical Generators
The pontine brainstem serves as the primary control center for REM sleep generation through specific neuronal populations:
The sublaterodorsal nucleus (human equivalent of the rat pons structure) and precoeruleus region contain the critical "REM-on" neurons that actively generate REM sleep when disinhibited 1
These REM-on neurons are glutamatergic and project to multiple targets to produce the characteristic features of REM sleep, including muscle atonia and cortical activation 1
The pedunculopontine tegmental nucleus (PPT) and laterodorsal tegmental nucleus (LDT) contain cholinergic neurons that promote REM sleep by inhibiting REM-off cells 1, 2
Regulatory "Flip-Flop" Switch Mechanism
REM sleep is controlled by reciprocally inhibitory neuronal populations that function as a switch:
The "REM-off" area includes the ventrolateral periaqueductal grey matter and lateral pontine tegmentum, which contain GABAergic neurons that suppress REM sleep 2
The "REM-on" area (sublaterodorsal nucleus and precoeruleus) and "REM-off" area are reciprocally interconnected and mutually inhibit each other through GABAergic projections, creating a bistable switch 2
When REM-on neurons overcome inhibition from REM-off neurons, REM sleep is initiated and maintained 2
Modulatory Systems from Other Brain Regions
While the pons generates REM sleep, multiple brain regions modulate its occurrence:
The locus coeruleus (noradrenergic) and dorsal raphe nucleus (serotonergic) provide inhibitory modulation to REM-on neurons, suppressing REM sleep during wakefulness and NREM sleep 1, 2
The lateral hypothalamus contains orexinergic (hypocretin) neurons that activate REM-off areas, thereby inhibiting REM sleep 1, 2
The ventrolateral preoptic nucleus contains GABAergic and galanin-ergic neurons that inhibit REM-off areas, facilitating REM sleep onset 1, 2
The suprachiasmatic nucleus (hypothalamus) serves as the master circadian pacemaker that times REM sleep occurrence within the 24-hour cycle 1, 3
Descending Pathways for REM Sleep Features
The pontine REM generators project to create the characteristic features of REM sleep:
Descending pathways from the rostral pons to the medulla produce muscle atonia through both cholinoceptive and cholinergic pathways that inhibit motor neurons 4
Phasic muscle activity during REM sleep (like rapid eye movements) originates from brainstem excitatory drives that temporarily overcome tonic inhibition 4
Clinical Implications
Understanding REM sleep origins is critical for diagnosing and treating REM sleep behavior disorder (RBD):
Pathology in the sublaterodorsal nucleus or precoeruleus region, or in their modulatory inputs, can lead to RBD by disrupting the normal muscle atonia of REM sleep 1
Medications affecting serotonin, norepinephrine, acetylcholine, dopamine, or hypocretin systems can alter REM sleep because these neurotransmitters modulate the pontine REM generators 1
The complexity of REM sleep generation explains why multiple medication classes can both cause and treat RBD, depending on which component of the system they affect 1