# Non-Neuronal Sleep/Wake Control in Cortex

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2022 · $406,281

## Abstract

Sleep and wake are critical for animal survival, but the mechanisms by which the brain coordinates
switching between these brain states, from brainstem to cortex, remains unclear. Neuromodulatory signaling
circuits are essential systems for brain state switching, both in sleep/wake and in other contexts. In the current
proposal, we explore the role of one of these neuromodulators—histamine—in the regulation of sleep and
wake in the cerebral cortex. Although histamine has long been known as a wake-promoting neuromodulator, it
is relatively understudied compared to others, so our understanding of its cellular and circuit mechanisms of
action is still in the early stages. Here, we take a holistic perspective of the cell types involved in sleep/wake
circuits, and ask how the largest class of non-neuronal cells in the brain, astrocytes, are involved in sending
and responding to histaminergic signals in the cortex. We aim to address gaps in our knowledge of sleep/wake
dynamics, histaminergic signaling, and astrocytic regulation of neural circuits by uncovering critical cell
biological signaling systems in astrocytes. We apply advanced optical, electrophysiological, and neural
manipulation techniques to reveal how astrocytes may be integrating neuromodulatory signals in cortical
circuits and coordinating populations of neurons. Our main goals include: probing the cell biological
mechanisms by which histamine activates astrocytes, testing the spatiotemporal dynamics of histamine and
astrocytes to determine their causal relationships, and exploring the mechanisms by which astrocytes may
synchronize or desynchronize neuronal activity.

## Key facts

- **NIH application ID:** 10356161
- **Project number:** 5R01MH121446-03
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** GRAEME W DAVIS
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $406,281
- **Award type:** 5
- **Project period:** 2020-05-06 → 2025-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10356161

## Citation

> US National Institutes of Health, RePORTER application 10356161, Non-Neuronal Sleep/Wake Control in Cortex (5R01MH121446-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10356161. Licensed CC0.

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