Neural circuits underlying the acquisition and control of motor skills Much of our behavioral repertoire consists of learned motor skills, yet little is known about the neural mechanisms that underlie their acquisition and execution. We have recently discovered that motor cortex is required for learning but not for executing certain motor skills, suggesting an autonomous subcortical motor network capable of generating task-specific learned motor sequences. Importantly, motor cortex seems to be involved in ?tutoring? this subcortical network during learning. Here we will first explore the role of the basal ganglia, a collection of motor-related midbrain nuclei of great clinical significance, in the storage and execution of complex task-specific motor sequences. Specifically, we will test whether the part of the basal ganglia that receives input from motor cortex, the dorsolateral striatum (DLS), is essentially involved in producing the skills we train. We will do this by way of lesioning DLS and other parts of the basal ganglia in animals that have learned to master the task we train (Aim 1). We will further analyze how the striatum encodes the learned motor sequences, specifically testing the hypothesis that it encodes the detailed structure and kinematics of learned motor sequences (Aim 2). Lastly, we will test the idea that motor cortex is ?tutoring? the subcortical motor circuits during learning through its projections to the basal ganglia (Aim 3). We will explore these questions using a fully automated rodent training system we developed, in combination with a set-up for recording neural activity and behavior continuously over weeks and months in freely behaving rodents. Addressing the aims of our proposal will clarify the logic of how the mammalian motor system acquires and controls task-specific motor sequences, and delineate the roles of the BG and the corticostriatal pathway in these important processes, thus addressing fundamental questions in neuroscience with far-reaching implications for clinical practice and neurorehabilitation.

Public Health Relevance

The ability to learn and execute motor skills is central to our everyday existence. Our reliance on motor skills leaves us vulnerable to neurological disorders and strokes that affect the circuits involved in their acquisition and control. Our research goal is to elucidate how the mammalian motor system, specifically motor cortex and the basal ganglia, contribute to learning and producing motor skills. This work will inform the design of new therapeutics and neurorehabilitation paradigms for patients with motor disabilities.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS099323-05
Application #
9961695
Study Section
Sensorimotor Integration Study Section (SMI)
Program Officer
Chen, Daofen
Project Start
2016-09-01
Project End
2021-06-30
Budget Start
2020-07-01
Budget End
2021-06-30
Support Year
5
Fiscal Year
2020
Total Cost
Indirect Cost
Name
Harvard University
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
082359691
City
Cambridge
State
MA
Country
United States
Zip Code
02138
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Dhawale, Ashesh K; Poddar, Rajesh; Wolff, Steffen Be et al. (2017) Automated long-term recording and analysis of neural activity in behaving animals. Elife 6:
Dhawale, Ashesh K; Smith, Maurice A; Ölveczky, Bence P (2017) The Role of Variability in Motor Learning. Annu Rev Neurosci 40:479-498