# RP4: Linking Spinal Circuits to Behavior

> **NIH NIH U19** · SALK INSTITUTE FOR BIOLOGICAL STUDIES · 2023 · $773,199

## Abstract

Project Summary: Project 4 – Linking Spinal Circuits to Behavior
Despite the critical role forelimb movements play in our interaction with the world, little is known about how
specific neural circuits control the precision, speed, and fidelity of these behaviors. While most studies of forelimb
movement explore descending motor command pathways, the neural architecture of the cervical spinal cord that
supraspinal pathways ultimately recruit to execute dexterous forelimb movement remains mysterious. To
address this challenge, two central questions will be explored: 1) How do spinal networks that control rhythmic
pattern generation transition to coordinate non-rhythmic movements, which represent the majority of forelimb
motor behaviors? 2) How are these spinal circuits modified to control more complex joint movements and achieve
forelimb dexterity? Project 4 will bridge the anatomical, physiological, and molecular delineation of motor
circuits in the cervical spinal cord (Projects 2 and 3) with the forelimb behaviors they control. This
functional information will be used to develop models of spinal circuitry (Project 1) and build a
multimodal atlas of the cervical spinal cord (Data Core).
While genetic tools in mice have provided a means to define the organization and function of neural circuits,
major impediments to exploring the neural basis of skilled forelimb control remain: a) standardized assays for
probing mouse forelimb behaviors are few; and b) the lack of electrophysiological access to spinal motor circuits
in behaving animals precludes the ability to define how the activity of these circuits corresponds with behavioral
output. This Project proposes three major Aims that will address these obstacles. Aim 1 will develop and apply
sensitive behavioral assays and electromyography (EMG) recording from forelimb muscles to provide more
comprehensive and empirical experimental access to motor control across forelimb joints during defined
behaviors. Aim 2 will apply modern molecular-genetic perturbation to investigate the functional organization of
pre-motor interneuron networks that modulate the activity of forelimb motor neurons and orchestrate movement.
Aim 3 will develop novel approaches for recording from the spinal cord of animals performing forelimb
movements, overcoming a critical barrier to defining how spinal neural activity correlates with movement, and
how this activity is affected by targeted perturbation. By simultaneously examining each major step in the
pathway, from spinal neural circuit activity, to muscle recruitment, to limb kinetics and kinematics, this work will
generate a functional map of forelimb motor circuits and enable predictive models of forelimb control to be tested
and refined. Ultimately, these advances will provide insight into the neural roots of movement more generally,
and help to lay the foundation for better diagnosis and treatment of motor deficits caused by injury or disease.

## Key facts

- **NIH application ID:** 10696200
- **Project number:** 5U19NS112959-05
- **Recipient organization:** SALK INSTITUTE FOR BIOLOGICAL STUDIES
- **Principal Investigator:** EIMAN AZIM
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $773,199
- **Award type:** 5
- **Project period:** 2019-09-15 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10696200

## Citation

> US National Institutes of Health, RePORTER application 10696200, RP4: Linking Spinal Circuits to Behavior (5U19NS112959-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10696200. Licensed CC0.

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