This proposal is a neurophysiological study of the climbing fiber system's role in the cerebellar cortex and motor behavior. The global hypothesis underlying the grant is that the climbing fiber afferent system, possibly acting as an error signal, increases a Purkinje cell's responsiveness to mossy fiber input. The climbing fiber input to neighboring Purkinje cells is tightly correlated, resulting in an accentuation of the gain of a cerebellar cortical region. The altered Purkinje cell output from a cerebellar cortical region is hypothesized to modify motor behavior. Initial studies in acute cats will evaluate climbing fiber afferent modification of Purkinje cell responsiveness to mossy fiber input. Short and long term changes will be evaluated using analytical techniques designed to remove the simple spike signal from the background activity. These techniques will permit statistical evaluation of the changes in simple spike activity associated with climbing fiber afferent input. Using two models of behavior, locomotion in the premammillary cat and voluntary arm movements in the intact primate, the interaction between climbing fiber afferent input and Purkinje cell discharge will be evaluated. The evoked complex spike activity and associated changes in simple spike activity will be related to alterations in walking or limb movements. Statistical analyses are designed to evaluate the relationships between the complex spike discharge, simple spike activity and the movement kinematics. The inferior olive possesses an inherent tendency to oscillate. Acute cat studies will test whether the rhythmicity represents a brief, but stable limit cycle of a population of inferior olivary neurons. The resetting characteristics of spontaneous as well as evoked complex spike discharge will be evaluated and compared. In the primate movement studies the presence or absence of climbing fiber rhythmicity will be evaluated. Associated rhythmicity in the simple spike discharge, limb kinematics or EMG activity will be evaluated. Overall these studies will increase our understanding of the role of the climbing fiber afferent system in the cerebellar cortex and motor behavior.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS018338-07
Application #
3398383
Study Section
Neurology A Study Section (NEUA)
Project Start
1982-04-01
Project End
1990-03-31
Budget Start
1988-04-01
Budget End
1989-03-31
Support Year
7
Fiscal Year
1988
Total Cost
Indirect Cost
Name
University of Minnesota Twin Cities
Department
Type
Schools of Medicine
DUNS #
168559177
City
Minneapolis
State
MN
Country
United States
Zip Code
55455
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
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 (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
Lang, Eric J; Apps, Richard; Bengtsson, Fredrik et al. (2017) The Roles of the Olivocerebellar Pathway in Motor Learning and Motor Control. A Consensus Paper. Cerebellum 16:230-252
Popa, Laurentiu S; Streng, Martha L; Ebner, Timothy J (2017) Long-Term Predictive and Feedback Encoding of Motor Signals in the Simple Spike Discharge of Purkinje Cells. eNeuro 4:
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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