A central medullary circuit regulating REM sleep and pontine waves

Rapid-eye-movement (REM) sleep is a distinct behavioral state best known for its association with vivid dreaming in humans, as well as its theorized role in memory formation and consolidation. REM sleep is composed of tonic features such as hippocampal theta oscillations and skeletal muscle paralysis, which are interleaved with short-lived phasic events such as rapid eye movements, limb twitches, and spike-like pontine (P)-waves. Considered a key hallmark of REM sleep, P-waves are coupled with transient increases in theta power and frequency known as theta bursts, and they have been implicated in REM sleep-dependent memory processing. Yet despite their functional importance, little is known about the neural circuits underlying the regulation of P-waves, nor the extent to which these circuits interact and overlap with the networks generating REM sleep itself. Here, I identify a novel population of excitatory dorsomedial medulla (dmM) neurons expressing corticotropin-releasing-hormone (CRH) with a dual role in regulating both REM sleep and P-waves in mice. Calcium imaging revealed that dmM CRH neurons are selectively activated during REM sleep, and their activity within REM sleep episodes specifically correlates with P-waves and theta bursts. Minutes-long optogenetic stimulation of dmM CRH neurons robustly initiated and maintained REM sleep, while optogenetic inhibition truncated REM sleep episodes. In addition, brief optogenetic activation of the dmM CRH population reliably elicited P-waves and theta bursts, with the likelihood of P-wave induction depending on the phase, power, and frequency of the ongoing theta oscillations. Finally, chemogenetic manipulation of dmM CRH neurons bidirectionally modulated both REM sleep amount and P-wave frequency. Together, this work anatomically and functionally delineates a medullary hub for the control of both REM sleep and P-waves.

Author dc:creator

• Schott, Amanda

Advisor dc:contributor.advisor

• Weber, Franz, L

• Neuroscience and Neurobiology

Language dc:language.iso

en

Repository record dc:identifier.uri

https://repository.upenn.edu/handle/20.500.14332/59509

OAI identifier oai:identifier

oai:repository.upenn.edu:20.500.14332/59509