# Neural control of skilled movements: an ethological dissection of genetically tractable mammalian motor circuits

> **NIH NIH DP2** · SALK INSTITUTE FOR BIOLOGICAL STUDIES · 2022 · $570,000

## Abstract

Project Summary
 Of the diverse features of the mammalian motor repertoire, skilled limb movements have become some
of the more impressive and indispensable ways of interacting with the environment. The susceptibility of these
movements to neurodegenerative disease and injury underscores the need for a better understanding of how
neural circuits orchestrate these dexterous behaviors. This goal demands sophisticated experimental scrutiny
at both neural and behavioral levels, and while the emergence of genetic tools for monitoring and manipulating
neural circuits in mice has been transformative, the development of motor behavioral assays has not kept
pace. Typically, a single behavioral test is applied to the question at hand, precluding a more comprehensive
description of why relevant neural circuits have evolved their particular anatomical and functional attributes.
Moreover, in the study of limb motor control, primate-inspired behavioral paradigms tend to be applied to the
mouse by default, risking neglect of a more complete and naturalistic account of motor circuit function.
 Ethology emphasizes an unbiased study of behavior under natural conditions. This proposal describes
an ethological approach for the quantification and categorization of skilled limb movements in mice, enabling a
depth and breadth of behavioral analysis that more closely aligns with the complexity of the underlying neural
circuits. Several complementary approaches for unbiased behavioral quantification of mouse limb movements
in enriched environments will be developed in parallel: a set of optical techniques enabling automated three-
dimensional reconstruction of limb and digit posture and trajectory; and an approach that leverages advances
in the miniaturization of motion sensors for camera-free limb tracking that can be integrated seamlessly with
neural and electromyography (EMG) recordings. Through iterative refinement, this multifaceted strategy should
highlight the strengths and mitigate potential drawbacks of each tracking method, providing a suite of
complementary quantitative tools. Kinematic, kinetic, EMG and neural data collected across diverse behavioral
contexts will be used to guide machine learning-based classification of natural structure in limb movements
and in their underlying neural circuits. As a proving ground for how these naturalistic behavioral analyses can
be integrated with the genetic dissection of neural circuit function, a set of molecularly defined motor circuits
will be probed using novel optogenetic tools that permit selective inhibition at defined axon collateral terminals.
This combination of projection specific genetic perturbation and ethologically driven behavioral analyses will
provide a powerful lens through which to view the fine-grained functional organization of mammalian motor
circuits. More generally, this merging of molecular and systems neuroscience approaches will offer a novel
way to explore and compare fine motor control acro...

## Key facts

- **NIH application ID:** 9976305
- **Project number:** 4DP2NS105555-02
- **Recipient organization:** SALK INSTITUTE FOR BIOLOGICAL STUDIES
- **Principal Investigator:** EIMAN AZIM
- **Activity code:** DP2 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $570,000
- **Award type:** 4N
- **Project period:** 2017-09-09 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9976305

## Citation

> US National Institutes of Health, RePORTER application 9976305, Neural control of skilled movements: an ethological dissection of genetically tractable mammalian motor circuits (4DP2NS105555-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9976305. Licensed CC0.

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