# Neural circuit basis for neurovascular coupling

> **NIH NIH R01** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2024 · $510,125

## Abstract

Abstract
Neurovascular coupling (NVC) is the temporal relationship between neural activity and cerebral blood flow
(CBF). This neural-evoked hemodynamic response is fundamental to local cerebrovascular homeostasis and
is disrupted in cerebrovascular diseases, such as stroke, cerebral amyloid angiopathy, traumatic brain injury,
as well as Alzheimer's Disease. The neurons that express neuronal nitric oxide synthase (Nos1) are ideal
candidates for the regulation of NVC since nitric oxide (NO) is a very potent vasodilator. Our group has
recently developed a Tacr1CreER allele that enables the visualization and manipulation of these neurons. We
now have exciting preliminary data supporting the hypothesis that Tacr1 neurons mediate vasodilation. Here,
we propose to test this idea through a set of experiments that will: determine the relationship between Tacr1
neurons and blood vessels; examine causality in the regulation of NVC by Tacr1 neurons; and investigate the
underlying circuitry. These experiments include correlative studies that will establish whether the structure
(place) and function (activity) of Tacr1 neurons positions them to regulate CBF. We will also use optogenetic
approaches and laser Doppler flowmetry (LDF) to record CBF in awake behaving mice to test whether Tacr1
neurons necessary and sufficient for vasodilation. Finally, we will use a combination of optogenetic
manipulation, GCaMP6f-, and 2P-imaging to elucidate the underlying circuitry of NVC. Overall, our proposal
will address a critical gap in knowledge with respect to the specific neural mechanisms that underlie the BOLD
signal, which is a widely used, but poorly understood research and clinical tool. Moreover, this insight into
NVC is fundamental to our understanding of the pathogenesis of common cerebrovascular diseases and the
advancement of pharmacotherapeutics targeting cerebral perfusion.

## Key facts

- **NIH application ID:** 10764913
- **Project number:** 5R01NS119410-04
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** Sarah Elizabeth Ross
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $510,125
- **Award type:** 5
- **Project period:** 2021-02-15 → 2026-01-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10764913

## Citation

> US National Institutes of Health, RePORTER application 10764913, Neural circuit basis for neurovascular coupling (5R01NS119410-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10764913. Licensed CC0.

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