# Circuit Mechanisms Encoding Homeostatic Sleep Drive

> **NIH NIH R01** · JOHNS HOPKINS UNIVERSITY · 2020 · $358,203

## Abstract

Project Summary
Homeostasis is a fundamental physiological property, maintaining crucial state variables within a specific range
for the viability and fitness of animals. Homeostatic mechanisms are also important for motivated behaviors,
such as feeding or sleep. For example, prolonged wakefulness increases sleep drive (sleep pressure), leading
to an increase in sleep amount and/or depth (sleep rebound). The cellular and molecular mechanisms
underlying the homeostatic regulation of sleep remain unclear, and we have recently identified a novel neural
circuit that encodes sleep drive. Although sleep drive is widely assumed to inevitably increase with greater
wakefulness, exceptions to this rule exist in nature, particularly under conditions of high arousal. We
hypothesize that specific signaling mechanisms act on this homeostatic circuit to suppress the accumulation
and/or release of sleep drive. The overall goal of this proposal is to leverage these new findings to unravel the
molecular and cellular mechanisms underlying sleep homeostasis. In addition, emerging data suggest an
important role for glia in the homeostatic regulation of sleep. Thus, we propose to carry out the following aims:
1) characterize the signaling pathways acting on this novel circuit to regulate sleep drive; 2) characterize the
circuit mechanisms acting downstream of this sleep homeostatic circuit to promote sleep; and 3) investigate a
specific role for glia in the homeostatic regulation of sleep. To carry out these studies, we will use a variety of
approaches, including behavioral assays, molecular genetic analyses, immunohistochemistry, functional
imaging, and patch-clamp electrophysiology. These studies should reveal new insights into how sleep is
homeostatically regulated. Insomnia and disorders of pathologic sleepiness are common and often associated
with substantial morbidity. A better understanding of the mechanisms underlying sleep homeostasis may help
in our search for novel treatments for both pathologic sleepiness and insomnia.

## Key facts

- **NIH application ID:** 9922377
- **Project number:** 5R01NS100792-04
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Mark N Wu
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $358,203
- **Award type:** 5
- **Project period:** 2017-08-15 → 2021-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9922377

## Citation

> US National Institutes of Health, RePORTER application 9922377, Circuit Mechanisms Encoding Homeostatic Sleep Drive (5R01NS100792-04). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/9922377. Licensed CC0.

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