# Synaptic mechanisms of functional recovery after stroke

> **NIH NIH P20** · WEST VIRGINIA UNIVERSITY · 2024 · $341,735

## Abstract

Remapping of function after stroke relies on the rewiring of cortical circuitry. These structural 
modifications of circuits likely depend on nanoscale alteration in the molecular architecture of individual 
synapses that generate alternate connectivity and strengthen surviving contacts. NMDA- and AMPA-type 
glutamate receptors play critical roles in regulating structural and functional plasticity of synapses. 
Following a stroke, the signaling via AMPARsand NMDARs changes, likely due to changes in their 
nanoscale localization. The small size of synapses has prevented us from understanding how synaptic 
nano-architecture is altered by stroke and how nanoscale synaptic changes might lead to functional 
recovery, limiting our ability to target synapses for stroke intervention. Our proposal seeks to break down 
this barrier by combining state-of-the-art STEDsuper-resolution imaging with behavioral analyses of 
sensorimotor function in the mouse model of stroke. Our preliminary data indicate that AMPARsand 
NMDARs exhibit distinct organizational principles relative to spine size and presynaptic release sites, 
suggesting that the exact set of nanoscale rules governs synaptic transmission and plasticity. We will 
test the hypothesis that precise nanoscale remodeling of individual spine synapses underlies the 
functional recovery after stroke. In aim 1, we will determine how changes in pre- and post-synaptic 
nano-architecture on cortical pyramidal neurons are linked to functional recovery after stroke. By imaging 
the organization of scaffolding (PSD-95 and Bassoon) and functional (AMPARs, NMDARs, Munc-13) 
components of synapses in early and late phases of recovery after stroke, we will establish how changes 
in synaptic nano-architecture relate to the recovery of sensorimotor function in both young and old mice. 
In aim 2, we will determine the role of ephrin-B3 on the remodeling of spine nano-architecture on cortical 
pyramidal neurons during stroke recovery. Testing ephrin-B3 null mice in sensorimotor behavioral 
paradigms, we will determine whether ephrin-B3 is required for the functional recovery after stroke. 
Finally, using two-photon and STEDimaging of dendritic spines in the somatosensory cortex, we will 
determine whether ephrin-B3 regulates synaptic remodeling after stroke. Novel molecular insights 
gained from this research will improve our understanding of stroke pathology while providing 
mechanistic underpinnings into functional recovery.

## Key facts

- **NIH application ID:** 11128397
- **Project number:** 5P20GM109098-10
- **Recipient organization:** WEST VIRGINIA UNIVERSITY
- **Principal Investigator:** Martin Hruska
- **Activity code:** P20 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $341,735
- **Award type:** 5
- **Project period:** 2014-09-08 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11128397

## Citation

> US National Institutes of Health, RePORTER application 11128397, Synaptic mechanisms of functional recovery after stroke (5P20GM109098-10). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/11128397. Licensed CC0.

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