The long term objective of this word is to define the role of the cerebellar cortex in voluntary motor behavior. Understanding normal function is an absolute requirement for understanding the crippling movement abnormalities that result from - cerebellar disease. This proposal 5 specific goals focus on defining both the kinematic and dynamic parameters - of arm movements encoded in the discharge of Purkinje cells. In visually guided, two-dimensional, multijoint arm movements, the discharge of paravermal and hemispheral Purkinje cells in the rhesus monkey will be studied in various tasks designed to vary different movement parameters while holding others constant.
Four specific aims are proposed: 1) Determine the velocity sensitivity of Purkinje cells in 2-dimensional tracking movements. Two series of tracking tasks are proposed, one based on tracking targets moving at constant velocities and the other on tracking targets moving with a bell shaped velocity profile. The first task allows the manipulation of movement velocity in relationship to movement-direction keeping acceleration and position constant. The second tracking task will permit sorting out the relative contributions of three highly coupled parameters: velocity, distance, and movement time. 2) Determine the contribution of multiple parameters of movement, including kinematic and dynamic variables, to the simple-and complex spike discharge of Purkinje cells. Two dimensional, horizontal reaching movements of different direction and distance restricted to the elbow and shoulder will be used to quantify not only the kinematics of the hand, but the underlying joint motions and torques. An emphasis will be placed on whether the purkinje cell discharge is more tightly coupled to the movements in relation to the hand motions or in relationship to the motions of the individual points. 3) Determine if the Purkinje cell discharge evoked in response to a perturbation encodes information about the direction and distance of the error or perturbation. In this task, the animal will move from a start box to a target box. As the animal reaches the target box, the target box will be displaced to a new position. Different directions and distances of this target box perturbation will be evaluated. The simple and complex spikes evoked by the perturbation will be analyzed for both directional and distance dependency. 4) Determine whether Purkirne cell discharge is encoded in a motor or sensory reference frame using a vasomotor dissociation task. Monkeys will be trained to produce movements in which the physical trajectory of the hand and the sensory counterpart of that trajectory are equivalent and when the motor and sensory representations are dissociated. These studies will test directly whether the Purkinje cell responses are organued in one or a combination of these reference frames.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Research Project (R01)
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Neurology A Study Section (NEUA)
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Baughman, Robert W
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University of Minnesota Twin Cities
Schools of Medicine
United States
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Hedges, Valerie L; Chen, Gang; Yu, Lei et al. (2018) Local Estrogen Synthesis Regulates Parallel Fiber-Purkinje Cell Neurotransmission Within the Cerebellar Cortex. Endocrinology 159:1328-1338
Streng, Martha L; Popa, Laurentiu S; Ebner, Timothy J (2018) Modulation of sensory prediction error in Purkinje cells during visual feedback manipulations. Nat Commun 9:1099
Streng, Martha L; Popa, Laurentiu S; Ebner, Timothy J (2017) Climbing fibers predict movement kinematics and performance errors. J Neurophysiol 118:1888-1902
Streng, Martha L; Popa, Laurentiu S; Ebner, Timothy J (2017) Climbing Fibers Control Purkinje Cell Representations of Behavior. J Neurosci 37:1997-2009
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Popa, Laurentiu S; Streng, Martha L; Hewitt, Angela L et al. (2016) The Errors of Our Ways: Understanding Error Representations in Cerebellar-Dependent Motor Learning. Cerebellum 15:93-103
Hewitt, Angela L; Popa, Laurentiu S; Ebner, Timothy J (2015) Changes in Purkinje cell simple spike encoding of reach kinematics during adaption to a mechanical perturbation. J Neurosci 35:1106-24
Cramer, Samuel W; Popa, Laurentiu S; Carter, Russell E et al. (2015) Abnormal excitability and episodic low-frequency oscillations in the cerebral cortex of the tottering mouse. J Neurosci 35:5664-79
Prosise, Jodi F; Hendrix, Claudia M; Ebner, Timothy J (2015) Joint angles and angular velocities and relevance of eigenvectors during prehension in the monkey. Exp Brain Res 233:339-50

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