The cerebellum is critical for learning of motor skills. Since the 60's and 70's, the field has been working within the framework of the cerebellar learning theory: climbing fiber inputs to the cerebellum signal errors in movements; the conjunction of climbing fiber inputs and parallel fiber activity leads to depression of the synapse from active parallel fibers onto Purkinje cell dendrites; this long-term depression (LTD) causes changes in the simple-spike firing of Purkinje cells on subsequent movements; and the change in cerebellar output causes gradual improvements in motor performance and eliminates motor errors. Subsequent behavioral and neural studies suggest that learning is mediated by multiple plasticity mechanisms at several brain sites. The present proposal uses the smooth pursuit eye movements of awake, behaving monkeys to understand how a full neural circuit single organizes motor skill learning. The proposal first will describe the time course of development of multiple components of behavioral learning, especially a component that requires repetition of learning stimuli to consolidate. Next, the proposed experiments will study neural correlates of the different components of learning in three different areas in the cerebellar circuit for pursuit eye movements; Purkinje cells in the floccular complex, their target neurons (FTNs) in the vestibular nucleus, and Purkinje cells related to pursuit in the oculomotor vermis. The floccular complex already has been implicated in a single-trial component of learning, and the proposed research will ask whether consolidated learning also is represented there. Recordings from the other areas will allow quantitative conclusions about the extent to which neural learning is localized in the floccular complex, and whether multiple components of learning evolve over different time courses at different sites in the circuit. Motor skill learning is an essential mechanism for allowing humans to relearn old movements after strokes, and for maintaining excellent motor function as the nervous system ages. An understanding of the neural circuit mechanisms of motor learning should facilitate clinical approaches in motor disorders and stroke.

Public Health Relevance

Motor skill learning is a critical function for the development of normal motor skills in children, for the retention of those skills as the brain ages, and for theray in relation to motor disorders. A better understanding of how and where the brain learns will be important for improving human health in cases of stroke, neuro- degenerative motor disease, and developmental motor disorders.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS092623-02
Application #
9230880
Study Section
Sensorimotor Integration Study Section (SMI)
Program Officer
Chen, Daofen
Project Start
2016-03-01
Project End
2020-11-30
Budget Start
2016-12-01
Budget End
2017-11-30
Support Year
2
Fiscal Year
2017
Total Cost
Indirect Cost
Name
Duke University
Department
Neurosciences
Type
Schools of Medicine
DUNS #
044387793
City
Durham
State
NC
Country
United States
Zip Code
27705