# Control of Sleep and General Anesthesia by the Median Preoptic Nucleus

> **NIH NIH R01** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2020 · $303,808

## Abstract

PROJECT SUMMARY / ABSTRACT
The relationship between sleep and general anesthesia is of great clinical relevance given the high prevalence
of patients with sleep disorders or insufficient sleep undergoing major surgery. To date, there is an incomplete
understanding of how mechanisms that regulate anesthetic state transitions and sleep homeostasis interact.
The preoptic region is a critical node for sleep regulation. The median preoptic nucleus (MnPO) regulates both
state transitions and sleep homeostasis, making it a key, yet virtually unexplored, substrate for sleep-
anesthesia interactions. Preliminary data obtained for this application suggest that distinct neuronal
subpopulations within MnPO control the transition to and from general anesthesia as well as sleep-wake
oscillations. Our long-term goal is to understand the neurobiological and clinical relationship between sleep
and general anesthesia. The goal of the proposed studies is to examine the role of GABAergic and
glutamatergic neurons in the MnPO and ventrolateral preoptic nucleus (VLPO) in sleep homeostasis and
general anesthesia. The proposed studies will use Designer Receptors Exclusively Activated by Designer
Drugs (DREADDs) to test the hypothesis that the MnPO is a primary site for arousal state control, and that
GABAergic and glutamatergic neurons in the MnPO regulate different aspects of sleep-wake states and
general anesthesia. Aim 1 will use DREADDs for selective activation of GABAergic and glutamatergic neurons
in the MnPO and VLPO to probe a causal relationship in controlling anesthetic induction, emergence, and post-
anesthesia sleep-wake behaviors. In a second set of experiments we will test whether DREADD
manipulations of MnPO and VLPO differentially alter corticocortical functional connectivity during wakefulness
and general anesthesia. Aim 2 will assess the role of GABAergic and glutamatergic neurons in the MnPO and
VLPO in sleep-wake regulation. Analysis of c-Fos immunoreactivity will reveal putative downstream targets of
MnPO and VLPO neurons in sleep/wake-related areas. Additional experiments will determine whether
activation of GABAergic neurons in the MnPO during general anesthesia can accelerate the anesthetic-
induced recovery of sleep debt accrued during previous sleep deprivation. The proposed experiments will
significantly advance our understanding of the mechanisms that regulate sleep-anesthesia interactions. These
data will also provide a novel paradigm of how a single brain region (in this case, the MnPO) can control
anesthetic induction and emergence through GABAergic and glutamatergic mechanisms, respectively.

## Key facts

- **NIH application ID:** 9963289
- **Project number:** 5R01GM124248-04
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** George Alexander Mashour
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $303,808
- **Award type:** 5
- **Project period:** 2017-08-15 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9963289

## Citation

> US National Institutes of Health, RePORTER application 9963289, Control of Sleep and General Anesthesia by the Median Preoptic Nucleus (5R01GM124248-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9963289. Licensed CC0.

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