# Neuronal and homeostatic regulation of sleep by the preoptic area and tuberomammillary nucleus

> **NIH NIH F31** · UNIVERSITY OF PENNSYLVANIA · 2021 · $46,036

## Abstract

PROJECT SUMMARY
While sleep is evolutionarily conserved across all animals studied, the precise function of sleep remains
unknown. It is vital that organisms receive an adequate amount of sleep, as sleep deprivation has profound
widespread physiological effects including cognitive impairment, compromised immune system function,
increased risk of cardiovascular disease, and in extreme cases can be fatal. In mammals, sleep is
characterized by transitions between rapid eye movement (REM) and non-REM (NREM) sleep states. Sleep
states and transitions between them are regulated by diverse neuronal populations found throughout the brain
and are under the influence of homeostatic pressure. While numerous sleep-active and wake-active brain
regions have been identified, it remains unknown how diverse neuronal populations coordinate their actions to
regulate sleep and wakefulness. The preoptic area (POA) of the hypothalamus contains sleep-active
GABAergic neurons and activation of their axons innervating the tuberomammillary nucleus (TMN) are critical
for sleep regulation. However, it is yet understood exactly how the activity of POA GABAergic axonal
projections to the TMN changes in response to increased sleep need and whether they are necessary to
integrate homeostatic pressure. Conversely, the TMN histaminergic neurons are wake-active and innervate the
POA. It is unknown how the activation of axonal projections of TMN histaminergic neurons or other neuronal
subtypes to the POA promotes wakefulness. Understanding how these cell-type specific nuclei coordinate as a
circuit via axonal projections will help elucidate the mechanism of sleep and wake regulation. The central
hypothesis of this proposal is that the POA and TMN contain cell-type specific reciprocal projections that
encode homeostatic sleep need and mediate sleep and wakefulness. To address this hypothesis, this proposal
will integrate genetic mouse models for specifically labeling specific cell types, in vivo and ex vivo
measurements of activity using fiber photometry, optrode and whole-cell patch-clamp recordings, and
optogenetic and chemogenetic techniques to modulate neuronal activity. Aim 1 will investigate the role of POA
GABAergic axonal projections to the TMN in sleep homeostasis. Aim 2 will define cell-type specific roles of
TMN axons innervating the POA in wake regulation. Together, these studies will reveal novel circuit
mechanisms by which the POA and TMN coordinate their activity during sleep/wake and periods of
homeostatic sleep pressure.

## Key facts

- **NIH application ID:** 10232008
- **Project number:** 1F31NS118963-01A1
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** John Maurer
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $46,036
- **Award type:** 1
- **Project period:** 2021-09-01 → 2025-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10232008

## Citation

> US National Institutes of Health, RePORTER application 10232008, Neuronal and homeostatic regulation of sleep by the preoptic area and tuberomammillary nucleus (1F31NS118963-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10232008. Licensed CC0.

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