Motor learning is the process by which movements become smooth and accurate through practice. Motor learning depends on a brain region called the cerebellum, and patients with cerebellar dysfunction have clumsy, uncoordinated movements. This project examines the error signals that guide motor learning. Which neurons in the cerebellum or related neural circuitry monitor the accuracy of a movement, and determine when the motor program controlling that movement needs to be updated? For decades it was thought that the "climbing fiber" input to the cerebellum from the inferior olive provided the sole instructive signal guiding motor learning. However, we recently showed that motor learning could be induced under training conditions that elicit no response in the climbing fibers. The proposed experiments analyze this climbing fiber-independent component of motor learning. In particular, we will examine the origin of the instructive signals controlling this component of learning, and we will determine which aspects of movement it can and cannot regulate. This project capitalizes on the experimental tractability of eye movements, in particular the vestibulo-ocular reflex (VOR), to analyze the neural mechanisms of motor learning. The VOR is a reflexive eye movement that reduces motion of visual images on the retina by evoking eye movements in the opposite direction to head movements. A form of motor learning, known as VOR adaptation, calibrates the VOR by gradually correcting the reflex when image motion is persistently associated with head turns. VOR adaptation is essential for ensuring adequate visual acuity during head turns and for restoring proper motor and perceptual orientation in space in response to changes in the organism or its environment, such as occur with growth and development, aging, injury to the peripheral or central nervous system or the donning of a new pair of spectacles.

Public Health Relevance

This project will improve our understanding of the neural mechanisms controlling the induction of learning. This improved understanding should facilitate the design of effective remediation strategies for disorders of learning and memory and rehabilitation strategies for CNS or peripheral injury.

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Research Project (R01)
Project #
5R01DC004154-13
Application #
8604386
Study Section
Neurobiology of Learning and Memory Study Section (LAM)
Program Officer
Platt, Christopher
Project Start
1999-09-30
Project End
2015-01-31
Budget Start
2014-02-01
Budget End
2015-01-31
Support Year
13
Fiscal Year
2014
Total Cost
$308,229
Indirect Cost
$123,099
Name
Stanford University
Department
Biology
Type
Schools of Medicine
DUNS #
009214214
City
Stanford
State
CA
Country
United States
Zip Code
94305
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
Shin, Soon-Lim; Zhao, Grace Q; Raymond, Jennifer L (2014) Signals and learning rules guiding oculomotor plasticity. J Neurosci 34:10635-44
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
Guo, Cong C; Raymond, Jennifer L (2010) Motor learning reduces eye movement variability through reweighting of sensory inputs. J Neurosci 30:16241-8
Ke, Michael C; Guo, Cong C; Raymond, Jennifer L (2009) Elimination of climbing fiber instructive signals during motor learning. Nat Neurosci 12:1171-9
Katoh, Akira; Jindal, Jenelle A; Raymond, Jennifer L (2007) Motor deficits in homozygous and heterozygous p/q-type calcium channel mutants. J Neurophysiol 97:1280-7
Kimpo, Rhea R; Raymond, Jennifer L (2007) Impaired motor learning in the vestibulo-ocular reflex in mice with multiple climbing fiber input to cerebellar Purkinje cells. J Neurosci 27:5672-82
Boyden, Edward S; Katoh, Akira; Pyle, Jason L et al. (2006) Selective engagement of plasticity mechanisms for motor memory storage. Neuron 51:823-34
Kimpo, Rhea R; Boyden, Edward S; Katoh, Akira et al. (2005) Distinct patterns of stimulus generalization of increases and decreases in VOR gain. J Neurophysiol 94:3092-100

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