# Inhibitory Neuron Sub-populations and Their Influence on Hemodynamic Imaging

> **NIH NIH R01** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2024 · $515,456

## Abstract

PROJECT SUMMARY/ABSTRACT
Neuronal activity actively modulates local cerebral vasculature. This neuro-vascular interaction is the foundation
of imaging studies of human brain function in health and disease. These studies are routinely performed while
subjects perform tasks (evoked activity) or lie resting (task-free or resting-state activity), and they assume that
imaging signals loyally reflect local neuronal activity. However, the neuro-vascular signaling mechanism is
complex and instances of uncoupling have been reported, limiting the interpretability of these studies. Recent
reports have shown that different types of neurons can regulate local blood supply stronger than others,
especially inhibitory neurons. These findings underscore the need to understand the vaso-regulatory roles of
different neuronal populations, especially considering that neurological disorders have been associated with
dysfunction of specific inhibitory neuron sub-populations. The goal of this proposal is to determine the role of
different sub-populations of inhibitory neurons on the regulation of local blood flow during evoked stimulation as
well as during resting-state activity periods. Experiments will be performed using unique transgenic mouse
models. In addition, we will determine whether these findings generalize over different cortical regions and
explore the translatability of these findings to human subjects by comparing the distribution of inhibitory neurons
that strongly regulate local blood flow in targeted regions of mouse and human brains. Our group has extensive
multi-modal expertise in neuro-vascular (and neuro-metabolic) physiology, including the models and techniques
proposed, and we are uniquely positioned to successfully complete the aims of this project. We will achieve
these goals through three aims: (Aim 1) Determine which inhibitory neuron sub-types strongly regulate local
blood flow changes evoked by optogenetic stimulation in different cortical regions; (Aim 2) Determine whether
the same sub-population of inhibitory neurons regulate local blood flow changes during ongoing awake activity
periods; and (Aim 3) Determine whether the sub-populations of inhibitory neurons identified in Aims 1 and 2 are
similarly distributed across the targeted regions of mouse and human brains. Since inhibitory neurons shape
network activity, these studies will detail the impact of specific inhibitory neuronal sub-type function and
dysfunction on local blood supply and hemodynamic-based imaging signals, expanding the interpretability and
clinical utility of human brain imaging studies in health and disease.

## Key facts

- **NIH application ID:** 10778541
- **Project number:** 5R01NS117515-04
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** ALBERTO L VAZQUEZ
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $515,456
- **Award type:** 5
- **Project period:** 2021-03-15 → 2026-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10778541

## Citation

> US National Institutes of Health, RePORTER application 10778541, Inhibitory Neuron Sub-populations and Their Influence on Hemodynamic Imaging (5R01NS117515-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10778541. Licensed CC0.

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