# OPTOGENETIC MAPPING OF CELL SPECIFIC CONNECTIONS IN THE MOUSE BRAIN AFTER STROKE

> **NIH NIH R01** · WASHINGTON UNIVERSITY · 2021 · $418,887

## Abstract

PROJECT SUMMARY/ABSTRACT
The goal of the current proposal is to determine how molecular- and systems-level mechanisms of brain repair
interact to influence behavioral recovery after focal ischemia in mice. Stroke causes direct structural damage to
local circuits and indirect functional damage to global networks that can result in behavioral deficits spanning
multiple domains. Neuroplasticity after stroke involves molecular changes within perilesional tissue that can be
influenced by distant regions spared from injury. At the systems level, functional magnetic resonance imaging
has revealed that recovery from stroke is associated with functional reorganization of the brain through the
formation of new or alternative circuits. Directly impacted brain regions remap to adjacent tissue in concert with
behavioral recovery. More globally, patterns of resting-state functional connectivity gradually normalize in
patients experiencing good recovery. While functional neuroimaging studies in humans and animal models
consistently demonstrate local and global changes in functional brain organization after stroke, it is unknown
how these processes interrelate to support behavioral recovery. Understanding how (or if) remapped brain
regions reintegrate into global networks to support recovery after stroke requires more direct examination of
evolving local and global connectivity structure. At the molecular level, limited data suggest that new axons
appear after stroke in periinfarct cortex and distant, homotopic contralateral cortex. Increased expression of
plasticity-associated genes are found in perilesional tissue including those involved in axonal sprouting. Growth
Associated Protein 43 (GAP-43) is an integral membrane protein found in axonal growth cones, synapses, and
widely induced after focal ischemia. This protein might drive anatomical connections within the periinfarct that
support functional restoration after stroke. However, the role of axonal sprouting in functional neuroplasticity
following focal ischemia has not been examined. We hypothesize that GAP-43-dependent axonal sprouting is
required for local circuit repair and reintegration into global networks, and this evolving process drives the degree
of behavioral recovery after stroke. We further hypothesize that axonal sprouting can be modulated by neural
activity in excitatory nodes functionally-connected to the site of injury, and these activity-dependent processes
depend on GAP-43. Critical barriers to testing this hypothesis in vivo have been the inability to serially examine
global network connectivity as it evolves with recovery, and longitudinally examine subunits of remapped circuits
as they change over time. We have overcome these barriers by integrating optical intrinsic signal imaging with
optogenetics to probe local circuit connectivity more directly. We will use this technology to determine: 1) how
the reemergence of local circuits and global networks relate to functional recovery fol...

## Key facts

- **NIH application ID:** 10201764
- **Project number:** 5R01NS102870-04
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** ADAM Q BAUER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $418,887
- **Award type:** 5
- **Project period:** 2018-09-30 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10201764

## Citation

> US National Institutes of Health, RePORTER application 10201764, OPTOGENETIC MAPPING OF CELL SPECIFIC CONNECTIONS IN THE MOUSE BRAIN AFTER STROKE (5R01NS102870-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10201764. Licensed CC0.

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