# Spinal Effects of Cortical Stimulation: Mechanisms and Functional Impact

> **NIH NIH R01** · ALBANY RESEARCH INSTITUTE, INC. · 2020 · $767,934

## Abstract

Project Summary/Abstract
 Because activity-dependent plasticity is ubiquitous in the CNS, brain stimulation may have long-term effects on
areas to which the stimulated area connects. These effects have received little attention. Nevertheless, recent
appreciation of the long-term role of cortex in shaping spinal cord pathways suggests that the long-term spinal
effects of cortical stimulation are likely to be substantial. In fact, weak electrical cortical stimulation (ECS) of
rat sensorimotor cortex has lasting spinal effects. Three months after ECS ends, GABA receptors in spinal
motoneurons remain decreased and the H-reflex (analog of the spinal stretch reflex) remains increased.
 This proposal seeks to determine in rats how ECS produces these spinal effects and to characterize the
effects on physiological, anatomical, and molecular levels. Preliminary studies support the hypothesis that the
spinal effects occur because ECS excites corticospinal tract (CST) neurons that synapse on spinal GABAergic
interneurons that synapse on soleus motoneurons, that this input reduces GABA metabotropic receptors and
thereby modifies motoneuron properties so as to increase the H-reflex (and also affect other spinal circuits), and
that specific gene activations underlie these effects. Two specific aims test this hypothesis.
 The first aim is to determine how ECS parameters affect its impact on the spinal cord and to define the
responsible descending pathway. ECS will be given by epidural electrodes. Pathway lesions and anatomical
tracers will identify the key pathway and its spinal targets. Based on initial data and other studies, the expectation
is that the CST is the essential pathway and that it connects to spinal motoneurons via GABAergic interneurons.
 The second aim is to characterize the short-term and long-term effects of ECS on spinal neurons and circuits
on physiological, anatomical, and transcriptional levels. These studies will: examine ECS impact on motoneuron
properties (e.g., firing threshold) and on spinal reflex pathways; explore immunohistochemically ECS impact on
GABAergic and other (e.g., glutamatergic) spinal interneurons and synapses and their receptors in soleus and
other spinal motoneurons; use next-generation sequencing methods (RNA-Seq) to identify ECS-induced changes
in gene expression in spinal motoneurons that correlate with and are likely to account for the changes in neuronal
properties, spinal circuit function, and immunohistochemical measures.
 In summary, this proposal uses a well-defined experimental model to explore the spinal effects of cortical
stimulation. By characterizing the nature and mechanisms of the spinal cord plasticity produced by this stimulation,
it should provide fundamental new insight into the wider effects of cortical stimulation, and also into how the
cortex modifies the spinal cord throughout life. Furthermore, the results should guide development of stimulation
protocols to further explore these effects, and stimulation...

## Key facts

- **NIH application ID:** 10156309
- **Project number:** 7R01NS110577-02
- **Recipient organization:** ALBANY RESEARCH INSTITUTE, INC.
- **Principal Investigator:** Jonathan Saul Carp
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $767,934
- **Award type:** 7
- **Project period:** 2019-09-30 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10156309

## Citation

> US National Institutes of Health, RePORTER application 10156309, Spinal Effects of Cortical Stimulation: Mechanisms and Functional Impact (7R01NS110577-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10156309. Licensed CC0.

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