REM Sleep at its Core - Circuits, Neurotransmitters, and Pathophysiology

Area of Science:

• Neuroscience
• Sleep Science

Background:

• Rapid eye movement (REM) sleep involves complex interactions between neurotransmitter systems in the brainstem, forebrain, and hypothalamus.
• The subcoeruleus nucleus (SubC), also known as the sublaterodorsal nucleus, is a core region active during REM sleep.

Purpose of the Study:

• To synthesize current understanding of the mechanisms generating healthy REM sleep.
• To explore how the SubC and interacting circuits regulate REM sleep features like muscle paralysis and cortical activation.
• To investigate how dysfunction in these circuits contributes to narcolepsy/cataplexy and REM sleep behavior disorder (RBD).

Main Methods:

• This review synthesizes existing research on REM sleep neurobiology.
• It focuses on the role of glutamatergic SubC neurons and their interactions with other neuronal populations.
• Analysis includes pathways involved in muscle atonia and sleep timing.

Main Results:

• Glutamatergic SubC neurons are hypothesized to regulate REM sleep and its key features.
• REM sleep paralysis is initiated by SubC activation of ventral medial medulla neurons, leading to GABA and glycine release onto motoneurons.
• REM sleep timing involves GABAergic neurons, melanin-concentrating hormone neurons, and cholinergic cells.

Conclusions:

• Disruptions in the communication within REM sleep regulatory circuits, particularly involving the SubC, are linked to narcolepsy/cataplexy and RBD.
• Further understanding of SubC-circuit interactions is crucial for developing therapeutic strategies for REM sleep disorders.