# Optogenetics to improve hand function after spinal cord injury.

> **NIH NIH R01** · UNIVERSITY OF WASHINGTON · 2020 · $497,136

## Abstract

Project Summary/Abstract
 Restoration of hand and arm function is the highest treatment priority for people with cervical spinal cord
injury. The goal of this research is to develop and test a novel method to improve recovery of hand and arm
function after spinal cord injury. We propose to use optogenetic stimulation of the cervical spinal cord to both
improve function and to uncover the mechanisms by which spinal cord stimulation leads to recovery.
 Our preliminary data demonstrate both a rapid and near complete recovery of forelimb function when
animals receive optogenetic spinal cord stimulation following a clinically-realistic cervical spinal cord contusion
injury. Optogenetic light stimulation may provide benefits by both directly activating neural circuits and also by
increase blood flow to the injured spinal cord. Here we propose to compare the functional recovery resulting
from optogenetic and electrical spinal cord stimulation, as well as the combination of electrical and light
stimulation delivered to naïve animals that do not express optogenetic proteins.
 Our experiments are enabled by a novel multifunctional electrode that permits both optical and electrical
stimulation to be delivered to the surface of the spinal cord in rodents. These flexible polymer electrodes will be
refined in Aim 1 to deliver chronic optogenetic and epidural electrical stimulation to the rat cervical spinal cord.
Thus all animals will be implanted with identical hardware prior to being randomized into treatment groups to
permit a direct comparison between optogenetic and electrical stimulation in Aim 2.
 We will use our established rat model of spinal contusion injury where animals are trained to perform
precision forelimb reaching to accurately quantify recovery of function after injury. Our collaborative team has
developed a reliable method of viral transduction of optogenetic proteins such that light-sensitive ion channels
are expressed in neurons of the non-transgenic rat cervical spinal cord. Following 6-weeks of treatment with
optogenetic and epidural electrical stimulation, we will explore the mechanisms by which each treatment leads
to prolonged recovery of forelimb function in Aim 3. We will perform terminal electrophysiology and record the
responses evoked by both optical and electrical stimulation in the same animals.
 Our preliminary data demonstrate an upregulation of axon growth following optogenetic stimulation. We will
use retrograde trans-synaptic tracing and histology to quantify new circuit formation bypassing the injury.
Labelled neurons will be co-localized with the neurons activated by optogenetic vs. epidural stimulation using
combined in-situ hybridization and immunohistochemistry to illuminate mechanisms of recovery.
 In summary, we propose to uncover the mechanisms by which optogenetic spinal cord stimulation leads to
nearly complete recovery of forelimb function following spinal cord injury. Once understood, we expect these
mechanism...

## Key facts

- **NIH application ID:** 10049377
- **Project number:** 1R01NS115025-01A1
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** Polina O Anikeeva
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $497,136
- **Award type:** 1
- **Project period:** 2020-09-15 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10049377

## Citation

> US National Institutes of Health, RePORTER application 10049377, Optogenetics to improve hand function after spinal cord injury. (1R01NS115025-01A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10049377. Licensed CC0.

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