Neural and computational mechanisms underlying the assembly of motor skills

NIH RePORTER · NIH · K99 · $88,506 · view on reporter.nih.gov ↗

Abstract

From typing on a keyboard to driving a car, motor skills are essential for our daily lives. Skills are modularly composed from a smaller set of natural motor elements – for instance individual keystrokes or arm movements – but little is known about the neural mechanisms that support this modular composition of motor elements into learned skills. The aim of this proposal is to understand how this modularity is achieved by interactions between the dorsolateral striatum and its motor cortical and dopaminergic inputs. We will gain new insights into this process through the development of a new technique, CAPTURE, which allows us to continuously track the position of a rat’s head, trunk, and limbs with superlative spatiotemporal resolution. By aligning motor elements across a skilled motor task and natural behaviors, CAPTURE allows us to precisely describe how a motor skill is assembled from pre-existing motor elements in an animal’s natural behavioral repertoire (Aim 1). We pair CAPTURE with a method recently developed in our laboratory that allows for continuous multi-unit neural recordings, a combination that allows us to precisely characterize how neural representations are reshaped across learning of a skill (Aim 2). Using this highly precise description of the skill learning process, we can then perform brain lesions and optogenetic stimulation to precisely identify the role of the motor cortex and phasic dopamine transients in skill learning (Aim 3). Completion of our aims should power new computational models of the neural basis of movement and skill learning and establish a new quantitative experimental platform for future studies. It should also provide new directions in the search for the circuit basis of human diseases of movement and behavior such as Parkinson’s disease and Obsessive Compulsive disorder. To guide my research and career development, I will by advised by a team of experienced mentors and experts in the basal ganglia, dopamine, and computational analysis. This team will advise my research project and career development through frequent meetings and be complemented by the tremendous scientific environment at Harvard University, which has numerous core facilities, scientists, and formal coursework to support my work. I will have the ability to grow as a mentor through undergraduate advising, and access to a broad curriculum in professional development. I will develop my professional network, presentation, and writing skills by presenting at local and international scientific meetings and writing scientific articles. My overall career goals are to establish a research laboratory at a major academic center and this mentored research project will establish new, unique experimental platform to differentiate my research program and develop several unique directions for research.

Key facts

NIH application ID
9993572
Project number
5K99NS112597-02
Recipient
HARVARD UNIVERSITY
Principal Investigator
Jesse D. Marshall
Activity code
K99
Funding institute
NIH
Fiscal year
2020
Award amount
$88,506
Award type
5
Project period
2019-08-15 → 2022-07-31