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.
The basal ganglia and dopamine systems are associated with a broad range of motor, learning and mental disorders such as Parkinson?s Disease, Huntington?s Disease and Obsessive Compulsive Disorder. The characterization of the neural and computational processes underlying skill learning we will perform, and the technology for precise kinematic tracking of behavior we develop will dramatically improve our understanding of the precise functional role of these circuits and provide means for improving diagnostics and therapeutics for afflicted patients.
