# REM sleep control by the sublaterodorsal tegmental nucleus glutamatergic neurons

> **NIH NIH R21** · SRI INTERNATIONAL · 2021 · $355,860

## Abstract

PROJECT SUMMARY/ABSTRACT
 Rapid eye movement (REM) sleep is characterized a desynchronized electroencephalogram (EEG) similar
to wakefulness, low electromyogram (EMG) indicative of skeletal muscle atonia, rapid eye movements,
autonomic instability, and reports of vivid dreaming. REM sleep disturbances contribute to a number of brain
diseases including the sleep disorders narcolepsy/cataplexy and REM sleep behavior disorder (RBD). REM
sleep is tightly controlled by a complex neural network in which the core circuits for REM sleep generation are
located in the brainstem. The sublaterodorsal nucleus (SLD) of the dorsolateral pons is a critical substrate
containing the core circuits. Subsets of SLD glutamatergic neurons are predominantly active during REM sleep
and promote the transition to REM sleep. Yet how these REM onset neurons perform these functions remains
poorly understood because we lack a deeper understanding of the molecular identities of these neurons and a
complete diagram of the circuit(s) in which they are located. This is largely due to the heterogenous nature of the
SLD region, which contains intermingled REM and wake-active neurons, and the limited precision and specificity
afforded by traditional techniques. The central goal of this project is to molecularly define the REM onset
populations within the SLD and to functionally evaluate their causal role in controlling REM sleep. Using two
unbiased high-throughput sequencing approaches, we will anatomically target SLD REM neurons and identify
their specific molecular markers (Aim 1). Using bidirectional optogenetic manipulation, we will then test whether
candidate neurons expressing these markers can promote REM sleep (Aim 2). Molecular identification of novel
REM neurons in the SLD will provide genetic access to the core circuits for REM sleep generation and thereby
advance our understanding of the circuit mechanisms underlying REM sleep control. The results of this project
should help open the door to the development of circuit-based therapeutic interventions for narcolepsy/cataplexy
and RBD.

## Key facts

- **NIH application ID:** 10285847
- **Project number:** 1R21NS123495-01
- **Recipient organization:** SRI INTERNATIONAL
- **Principal Investigator:** Peng Zhong
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $355,860
- **Award type:** 1
- **Project period:** 2021-08-16 → 2023-01-06

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10285847

## Citation

> US National Institutes of Health, RePORTER application 10285847, REM sleep control by the sublaterodorsal tegmental nucleus glutamatergic neurons (1R21NS123495-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10285847. Licensed CC0.

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