# Dissecting circuit and cellular mechanisms for limb motor control

> **NIH NIH RF1** · UNIVERSITY OF WASHINGTON · 2022 · $1,071,859

## Abstract

Motor neurons connect to muscles and comprise the major output of the nervous system. Patterns of
neural activity in motor neurons cause temporally precise muscle contractions, producing coordinated
and flexible behavior. These patterns are shaped by the connectivity and physiology of premotor circuits
in the spinal cord that synapse onto the motor neurons. Premotor circuits combine descending motor
commands with sensory feedback signals to drive motor neuron activity. How premotor networks are
structured to control motor output is not well understood, due in part to an incomplete inventory of spinal
cell types, and to the difficulties of recording neural activity in behaving animals. To address this gap, this
project aims to use Drosophila melanogaster as a model for investigating motor control and premotor
neural circuits. With an accessible and numerically compact nervous system, a large and growing suite
of genetic tools, and agile, limbed locomotion, Drosophila has the potential to provide insight into
fundamental problems of motor control. We introduce a task in which flies learn to generate specific
amounts of force to position the femur-tibia joint in different targets. The joint is controlled by twelve
neurons which can be genetically labeled for targeted neural recordings. Electrophysiological recordings
will reveal how the complete population of motor neurons function together to dynamically position the
leg and to sustain a given force output. These data will address long-standing hypotheses about how
premotor circuits recruit subsets of motor neurons and the degree to which that control is flexible. Then,
a new electron-microscopy level reconstruction of central locomotor circuits will allow identification of key
premotor neurons. Electrophysiological recordings of those premotor neurons during the behavioral task
will reveal their contributions to processing sensory feedback and to controlling leg force. These results
will provide a foundation for understanding how descending commands interact with internal models of
body state to control locomotion, a critical step toward achieving the long-term goals of designing
interventions for neuromuscular disorders and algorithms for controlling engineered systems.

## Key facts

- **NIH application ID:** 10522108
- **Project number:** 1RF1NS128785-01
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** John Tuthill
- **Activity code:** RF1 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $1,071,859
- **Award type:** 1
- **Project period:** 2022-08-17 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10522108

## Citation

> US National Institutes of Health, RePORTER application 10522108, Dissecting circuit and cellular mechanisms for limb motor control (1RF1NS128785-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10522108. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*