# Investigating descending control of walking

> **NIH NIH K99** · HARVARD MEDICAL SCHOOL · 2022 · $134,297

## Abstract

Project Summary/Abstract
Circuits in the brain control motor output to generate the precise behaviors required for survival. Dysfunction of
these circuits results in devastating movement disorders such as Parkinson’s disease and amyotrophic lateral
sclerosis. It is important to understand how the brain normally controls behavior by understanding what
features of motor output are encoded in individual neurons and how these representations are organized
across a neuronal population. This K99/R00 proposal will support Dr. Helen Yang in her pursuit to understand
motor control and allow her to acquire new skills in connectomics and modeling that will open up innovative
avenues of exploration of this problem. The experiments will be initiated during the mentored period (carried
out in Dr. Rachel Wilson’s lab in the Department of Neurobiology at Harvard Medical School) and continue in
Dr. Yang’s own lab upon securing an independent position. Dr. Yang’s long-term career goal is to understand
robustness and flexibility in motor control by exploring neural circuit architecture and encoding across
timescales, with the hope of providing insight into movement disorders and for the development of prosthetics
and robotics that recapitulate features of the brain’s control of motor action.
Dr. Yang’s current research has identified a number of descending neurons (DNs) whose activity is correlated
with specific features of walking behavior. DNs project from the brain to the nerve cord and are a key
bottleneck in the brain’s control of motor output. As such, understanding their encoding and organization will
reveal fundamental principles of motor control. Utilizing approaches including the monitoring and manipulation
of neural activity, behavior tracking, connetomics, and modeling, Specific Aim 1 will investigate how DNs
control turns during walking, and Specific Aim 2 will investigate how DNs control forward walking. During the
mentored phase of this proposal, Dr. Yang will focus on 3 specific DNs, but she will expand her studies to
additional DNs in the independent phase and examine how turning and forward DNs function together to
control walking.
Flexibility is a critical feature of motor actions, but how neuronal circuits implement it is still poorly understood.
Specific Aim 3, carried out during the independent phase, will investigate flexibility in walking by studying how
patterns of DN activity and recruitment change across behavioral contexts and internal states. Overall, the
experiments in this proposal should significantly advance understanding of how the brain controls motor output
and pave the way for Dr. Yang to secure an independent position in academia.

## Key facts

- **NIH application ID:** 10568039
- **Project number:** 1K99NS129759-01
- **Recipient organization:** HARVARD MEDICAL SCHOOL
- **Principal Investigator:** Helen Horan Yang
- **Activity code:** K99 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $134,297
- **Award type:** 1
- **Project period:** 2022-09-21 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10568039

## Citation

> US National Institutes of Health, RePORTER application 10568039, Investigating descending control of walking (1K99NS129759-01). Retrieved via AI Analytics 2026-08-11 from https://api.ai-analytics.org/grant/nih/10568039. Licensed CC0.

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