# The contribution of cortical NK1R/nNOS interneurons in neurovascular coupling

> **NIH NIH F31** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2020 · $45,520

## Abstract

Project Summary/Abstract
In cerebrovascular disorders, such as Alzheimer’s Disease and stroke, the ability to maintain normal cerebral
blood flow is compromised. Neurovascular coupling (NVC), the temporal relationship between neural activity
and cerebral blood flow, is thought to be disrupted in these conditions resulting in cerebral hypoperfusion and
cognitive dysfunction. As nitric oxide (NO) mediates vasodilation, the neurons that release (NO) are good
candidates as a major regulator of cerebral blood flow (CBF). We recently developed a new genetic tool—
NK1R-creER knockin mouse— that allows us to target and manipulate a specific subset of NO-generating
neurons (nNOS Type 1 neurons), and thus test the involvement of these cells in neurovascular coupling for the
first time. Here, we propose to test the specific hypothesis that nNOS Type 1 neurons receive excitatory
pyramidal input and mediate vasodilation. Aim 1 will investigate whether NK1R-creER cortical interneurons
receive excitatory pyramidal input using immunohistochemical approaches. Aim 2 will investigate whether
pyramidal neurons form functional synapses onto NK1R-creER cortical interneurons using
optogenetic approaches and slice electrophysiology. Lastly, Aim 3 will test whether NK1R-creER interneuron
activity is necessary and sufficient to increase cerebral blood flow in vivo using laser Doppler flowmetry.
Together, these experiments will investigate the circuits coupling neural activity and hemodynamics. 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:** 10091379
- **Project number:** 5F31NS106724-03
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** Catherine Faber Ruff
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $45,520
- **Award type:** 5
- **Project period:** 2018-03-01 → 2021-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10091379

## Citation

> US National Institutes of Health, RePORTER application 10091379, The contribution of cortical NK1R/nNOS interneurons in neurovascular coupling (5F31NS106724-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10091379. Licensed CC0.

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