# Examining the opposing roles of genetically distinct vagal afferents in sleep and wakefulness

> **NIH NIH F32** · STANFORD UNIVERSITY · 2020 · $65,310

## Abstract

Project summary|
Over 50 million people suffer from epilepsy worldwide resulting in massive health, social, and economic burdens.
While there is a growing need for improved anti-epileptic treatments, many of the current options are ineffective
and are coupled with harrowing side effects such as depression, nausea, and fatigue. Chronic vagus nerve
stimulation (VNS), in which an electrical implant stimulates the vagus nerve, can effectively treat epilepsy and is
one of the few alternatives for drug-resistant patients. Although it is widely believed that wake promoting vagal
subsets are responsible for the anti-epileptic effects, the identity, number, and valence of these subsets remains
unknown. Existing literature and ongoing studies in our own lab suggest that Neuropeptide Y Receptor 2 neurons
of the vagus sense hypoxia in the lung and promote wakefulness via dopaminergic neurons of the NTS.
Interestingly, literature also suggests that Glucagon-like Peptide 1 Receptor neurons innervating the stomach
may promote sleep following a meal. This proposal aims to couple recent genetic advances in targeting these
functionally distinct subsets with in vivo optical recording of neuronal activity and optogenetic circuit manipulation.
Specifically, hypoxia and food intake paradigms will be used to examine the state under which each neuronal
subset is engaged using fiber-photometry and genetically encoded calcium sensors. It also aims to examine the
capacity of each subset to promote wakefulness and attenuate seizures using optogenetic stimulation with
channelrhodopsins and fiberoptic implants. The findings will provide fundamental insight into the efficacy of VNS
and will provide a framework for future therapeutic innovation.

## Key facts

- **NIH application ID:** 9991288
- **Project number:** 1F32HL149458-01A1
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** Keith Richard Murphy
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $65,310
- **Award type:** 1
- **Project period:** 2020-07-01 → 2021-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9991288

## Citation

> US National Institutes of Health, RePORTER application 9991288, Examining the opposing roles of genetically distinct vagal afferents in sleep and wakefulness (1F32HL149458-01A1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/9991288. Licensed CC0.

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