# Excitability and plasticity alterations in a novel cerebellar stroke model

> **NIH NIH R01** · UNIVERSITY OF COLORADO DENVER · 2021 · $336,918

## Abstract

Project Summary
Development of therapies to treat the motor and cognitive deficits resulting from cerebellar stroke is hindered
by our current lack of mouse models to perform mechanistic translational studies. The current proposal
represents an important step forward, as we describe a new reproducible animal model of cerebellar stroke that
will be used to characterize the functional consequences of cerebellar ischemic stroke and begin to develop
strategies to improve functional outcomes. The objective of this proposal is to take advantage of our novel mouse
model of cerebellar stroke to elucidate network alterations that result from cerebellar stroke. Our central
hypothesis is that cerebellar ischemia causes thalamic hyperexcitability that disrupts sensory transmission and
causes excitatory: inhibitory imbalance. This hypothesis was developed on the basis of preliminary data
generated in the applicant’s laboratory. The rationale for the proposed research is that understanding network
disruptions will allow for the development of novel strategies to improve neurological function independent of
neuroprotective strategies that have failed to translate. The hypothesis will be tested by pursuing three specific
aims: 1) test if injury size and location correlates with chronic neurological impairments, 2) test if thalamic
excitability is altered after cerebellar stroke 3) determine alterations in excitatory and inhibitory synaptic inputs
that contribute to hippocampal plasticity deficits. Under the first aim, there is already strong preliminary data to
demonstrate motor and cognitive deficits in this novel mouse model of cerebellar stroke. Under the second and
third aims, we will use a neurophysiological to interrogate excitability and plasticity changes resulting from
cerebellar stroke. Preliminary data indicate that cerebellar ischemic stroke results in thalamic hyperexcitability
and impaired hippocampal synaptic plasticity. The approach is innovative as it provides an important tool for
performing mechanistic studies and moves away from neuroprotective strategies to focus on restoring
neurophysiological function at delayed time points. The proposed research is significant as it is expected to
expand understanding of network alterations that contribute to long-lasting deficits. Ultimately, such a
knowledge has the potential to inform the development of therapeutic strategies that improve neurological
function and quality of life for stroke patients.

## Key facts

- **NIH application ID:** 10241346
- **Project number:** 5R01NS105905-04
- **Recipient organization:** UNIVERSITY OF COLORADO DENVER
- **Principal Investigator:** Nidia Quillinan
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $336,918
- **Award type:** 5
- **Project period:** 2018-09-01 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10241346

## Citation

> US National Institutes of Health, RePORTER application 10241346, Excitability and plasticity alterations in a novel cerebellar stroke model (5R01NS105905-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10241346. Licensed CC0.

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