# Norepinephrine-dopamine interactions underlying arousal

> **NIH NIH R01** · EMORY UNIVERSITY · 2021 · $334,164

## Abstract

Project Summary/Abstract
Sleep disorders constitute a major public health problem in the United States, and abnormalities in arousal
often occur in concert with other neurological or neuropsychiatric diseases. The locus coeruleus (NE), the
major source of norepinephrine (NE) in the brain, promotes arousal, attention, and wakefulness, but the neural
substrates that transduce these actions of the LC have not been fully identified. One intriguing candidate is an
understudied population of wake-promoting dopamine (DA) neurons in the ventral periaqueductal gray
(vPAG). The LC projects to the vPAG, and our preliminary data indicate that NE provides excitatory drive onto
DA neurons in this brain region via α1-adrenergic receptors (α1ARs), suggesting that NE-DA interactions in the
vPAG may promote arousal. The goal of this proposal is to delineate this LC-vPAG circuit. In Aim 1, we will use
tract tracing and immunohistochemistry at the electron microscopic level to map the connections between the
LC and vPAG as well as specific localization of α1ARs. In Aim 2, we will use ex vivo slice electrophysiology to
determine the cellular mechanisms underlying the ability of NE to enhance excitatory drive onto vPAG DA
neurons. In Aim 3, we will use DREADD chemogenetics to assess the behavioral consequences of inhibiting or
stimulating various nodes of the LC-vPAG arousal circuit. These studies will define a novel arousal circuit and
identify candidate neuroanatomical and molecular targets for the treatment of both primary and disease-
associated deficits.

## Key facts

- **NIH application ID:** 10167796
- **Project number:** 5R01NS102306-05
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** Darlene A Mitrano
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $334,164
- **Award type:** 5
- **Project period:** 2017-07-01 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10167796

## Citation

> US National Institutes of Health, RePORTER application 10167796, Norepinephrine-dopamine interactions underlying arousal (5R01NS102306-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10167796. Licensed CC0.

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