Motor learning is the process by which movements become smooth and accurate through practice. Motor learning is important during early childhood development, and continues throughout adulthood, because the neural circuits controlling our movements need to be recalibrated in response to changes in the brain or body due to injury, disease, or the normal aging process. Motor learning depends on a brain region called the cerebellum, and patients with cerebellar dysfunction have clumsy, uncoordinated movements. One of the two main inputs to the cerebellum is the """"""""climbing fiber"""""""" input from the inferior olive in the brainstem. An influential theory of cerebellar function suggested that the climbing fibers carry the error signals that control motor learning. However, recent evidence suggests that motor learning can occur in the absence of instructive signals in the climbing fibers. Thus, there seems to be more than one way to implement motor learning in the brain. The goal of this project is to determine which aspects of motor learning are controlled by the activity of the climbing fibers, and which aspects of learning rely on other neural mechanisms. This question will be addressed by studying the eye movement responses to vestibular stimuli (i.e., the sensory signals encoding movements of the head) and their regulation by motor learning. Most, if not all, movements are guided by vestibular signals. The eye movement response to a vestibular stimulus is called the vestibulo-ocular reflex (VOR). This vestibular reflex functions to stabilize visual images on the retina, and is essential for maintaining good vision during movements of the body. Both the amplitude and the timing of the eye movements driven by the VOR can be adaptively modified by cerebellum-dependent learning, and thus the VOR serves as a model system for studying the neural mechanisms controlling movement amplitude and timing more generally.

Public Health Relevance

An important characteristic of neural circuits is their plasticity, their ability to change with experience and to compensate when injury or disease damages the nervous system. This project studies the error signals that guide the changes in a neural circuit during learning. An improved understanding of this process will inform the development of more effective interventions for a broad range of neurological and psychiatric disorders.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
3R01NS072406-02S2
Application #
8402694
Study Section
Sensorimotor Integration Study Section (SMI)
Program Officer
Gnadt, James W
Project Start
2010-09-01
Project End
2015-07-31
Budget Start
2011-08-01
Budget End
2012-07-31
Support Year
2
Fiscal Year
2012
Total Cost
$11,981
Indirect Cost
$4,350
Name
Stanford University
Department
Biology
Type
Schools of Medicine
DUNS #
009214214
City
Stanford
State
CA
Country
United States
Zip Code
94305
Suvrathan, Aparna; Payne, Hannah L; Raymond, Jennifer L (2018) Timing Rules for Synaptic Plasticity Matched to Behavioral Function. Neuron 97:248-250
Nguyen-Vu, Td Barbara; Zhao, Grace Q; Lahiri, Subhaneil et al. (2017) A saturation hypothesis to explain both enhanced and impaired learning with enhanced plasticity. Elife 6:
Suvrathan, Aparna; Payne, Hannah L; Raymond, Jennifer L (2016) Timing Rules for Synaptic Plasticity Matched to Behavioral Function. Neuron 92:959-967
Katoh, Akira; Shin, Soon-Lim; Kimpo, Rhea R et al. (2015) Purkinje cell responses during visually and vestibularly driven smooth eye movements in mice. Brain Behav 5:e00310
Shin, Soon-Lim; Zhao, Grace Q; Raymond, Jennifer L (2014) Signals and learning rules guiding oculomotor plasticity. J Neurosci 34:10635-44
Kimpo, Rhea R; Rinaldi, Jacob M; Kim, Christina K et al. (2014) Gating of neural error signals during motor learning. Elife 3:e02076
Guo, Christine C; Ke, Michael C; Raymond, Jennifer L (2014) Cerebellar encoding of multiple candidate error cues in the service of motor learning. J Neurosci 34:9880-90
Conner, Alana L; Cook, Karen S; Correll, Shelley J et al. (2014) Obscuring gender bias with ""choice"". Science 343:1200
Nguyen-Vu, T D Barbara; Kimpo, Rhea R; Rinaldi, Jacob M et al. (2013) Cerebellar Purkinje cell activity drives motor learning. Nat Neurosci 16:1734-6
Ke, Michael C; Guo, Cong C; Raymond, Jennifer L (2009) Elimination of climbing fiber instructive signals during motor learning. Nat Neurosci 12:1171-9