# Investigating Neural Processing of Cerebrovascular Dynamics via Calcium Imaging of Vascular Cells and Neurons, and by Optogenetic Vascular Pertubation, In Vivo

> **NIH NIH F31** · BROWN UNIVERSITY · 2022 · $23,688

## Abstract

PROJECT SUMMARY
 Understanding neural-vascular communication is vital to clinical and basic research. Perivascular neuron
(PVN) activity can drive cerebral blood vessel dynamics. However, the impact of vascular events on neural
activity has been only sparsely investigated. Our lab has found that a population of PVNs in primary
somatosensory cortex (SI) encode cerebrovascular activity in vivo. However, the nature of this encoding, and its
anatomical organization, is untested. Vessel-to-PVN signaling may support vascular homeostasis and rich
communication across systems. These signals are relevant for research using blood flow to map neural activity
(e.g., fMRI). Investigating perturbations of this signaling may elucidate mechanisms of cerebrovascular
disfunction (e.g., as in ischemia, Parkinson’s Disease, and M.S.).
 To analyze PVN encoding of vascular activity, I will use in vivo two-photon imaging of neural and vascular
cells, and optogenetics to perturb vessels and analyze the PVN response. In Aim I, I will test the hypothesis
that vascular-encoding PVNs occur commonly in SI, and their activity is organized by cortical layer and vascular
compartment, by expressing calcium indicators (jRGECO1a) in neurons and (GCaMP6f) in vascular endothelia
to image their activity simultaneously. My preliminary data identified spatially distinct calcium events in the
vascular signal that predict subsequent PVN activity. In this paradigm, the frequency of vessel responsive PVNs
will be categorized by their stereotyped activity and anatomical location. Preliminary data in our lab has also
shown that selective optogenetic vascular drive can modulate PVN activity. In Aim II, I will test the hypothesis
that PVNs driven by optogenetically evoked vascular diameter changes will also be organized anatomically by
their activity, that and their response to endogenous vascular events will parallel their response to optogenetic
vascular drive. I will optogenetically constrict SI blood vessels by driving endothelial channelrhodopsin, dilate
them with smooth muscle halorhodopsin, and evoke natural tactile driven functional hyperemia, to analyze the
responses of PVNs expressing GCaMP6s. In Aim III, I will test the hypothesis that PVN responses to
optogenetically driven vascular activity can be pharmacologically perturbed by TRPV4 and adenosine A1 receptor
antagonists, but that they are likely unaffected by blocking glutamatergic signaling. I will test this prediction by
evoking PVN responses to optogenetic vascular activity as in Aim II, and by exposing SI cortex to receptor
antagonists.
 Training Environment: This project will take place over three years in the Brown University
Neuroscience Graduate Program under the mentorship of Dr. Christopher Moore. The Research Training Plan
includes didactic professional, technical, and science writing training, as well as hands-on technical seminars.

## Key facts

- **NIH application ID:** 10458534
- **Project number:** 5F31NS115369-03
- **Recipient organization:** BROWN UNIVERSITY
- **Principal Investigator:** Eric M Klein
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $23,688
- **Award type:** 5
- **Project period:** 2020-08-01 → 2022-10-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10458534

## Citation

> US National Institutes of Health, RePORTER application 10458534, Investigating Neural Processing of Cerebrovascular Dynamics via Calcium Imaging of Vascular Cells and Neurons, and by Optogenetic Vascular Pertubation, In Vivo (5F31NS115369-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10458534. Licensed CC0.

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