The objective of the proposed research is to understand the on-line operation of intermediate cerebellar networks during the motor control and learning of protective eyelid movements. This will be studied using the model of classically conditioned eyeblinks. A series of studies will be performed in rabbits to characterize the function of the inferior olive in movement control and in the acquisition of anticipatory protective reflexes. The proposed research is based on the general hypothesis that the cerebellum, together with extra-cerebellar circuits, is responsible for recognizing a threatening environmental situation and generating adaptive anticipatory behavior. The unique feature of these proposed experiments is their use of an innovative method for manipulating specific synaptic inputs to central neurons without affecting spontaneous tonic activity of investigated neural networks. The first experiments will examine the specific role of sensory signals, carried from the inferior olive to the cerebellum, in the expression and retention of learned movements. In the second series of experiments, the role of the cerebellar inferior olivary input in conditioned response acquisition will be examined. This latter research represents a fundamental test of the popular cerebellar learning hypothesis. The results of this research are important for understanding the mechanisms related to the acquisition and retention of anticipatory defensive behaviors, and also for improving the rehabilitation of patients with deficits in sensorimotor integration through the understanding of the mechanisms underlying motor learning and recovery of motor function.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS036210-13
Application #
7806480
Study Section
Sensorimotor Integration Study Section (SMI)
Program Officer
Chen, Daofen
Project Start
1998-07-20
Project End
2012-04-30
Budget Start
2010-05-01
Budget End
2012-04-30
Support Year
13
Fiscal Year
2010
Total Cost
$313,465
Indirect Cost
Name
Iowa State University
Department
Other Basic Sciences
Type
Schools of Veterinary Medicine
DUNS #
005309844
City
Ames
State
IA
Country
United States
Zip Code
50011
Carrel, Andrew J; Zenitsky, Gary D; Bracha, Vlastislav (2013) Blocking glutamate-mediated inferior olivary signals abolishes expression of conditioned eyeblinks but does not prevent their acquisition. J Neurosci 33:9097-103
Perciavalle, Vincenzo; Apps, Richard; Bracha, Vlastislav et al. (2013) Consensus paper: current views on the role of cerebellar interpositus nucleus in movement control and emotion. Cerebellum 12:738-57
Zbarska, Svitlana; Bracha, Vlastislav (2012) Assessing the role of inferior olivary sensory signaling in the expression of conditioned eyeblinks using a combined glutamate/GABAA receptor antagonist protocol. J Neurophysiol 107:273-82
Carrel, Andrew J; Zbarska, Svitlana; Zenitsky, Gary D et al. (2012) A trigeminal conditioned stimulus yields fast acquisition of cerebellum-dependent conditioned eyeblinks. Behav Brain Res 226:189-96
Parker, Krystal L; Zbarska, Svitlana; Carrel, Andrew J et al. (2009) Blocking GABAA neurotransmission in the interposed nuclei: effects on conditioned and unconditioned eyeblinks. Brain Res 1292:25-37
Bracha, V; Zbarska, S; Parker, K et al. (2009) The cerebellum and eye-blink conditioning: learning versus network performance hypotheses. Neuroscience 162:787-96
Parker, Krystal L; Bracha, Vlastislav (2009) Inactivating the middle cerebellar peduncle abolishes the expression of short-latency conditioned eyeblinks. Brain Res 1303:32-8
Zbarska, Svitlana; Bloedel, James R; Bracha, Vlastislav (2008) Cerebellar dysfunction explains the extinction-like abolition of conditioned eyeblinks after NBQX injections in the inferior olive. J Neurosci 28:10-20
Zbarska, S; Holland, E A; Bloedel, J R et al. (2007) Inferior olivary inactivation abolishes conditioned eyeblinks: extinction or cerebellar malfunction? Behav Brain Res 178:128-38
Nilaweera, W U; Zenitsky, G D; Bracha, V (2006) Inactivation of cerebellar output axons impairs acquisition of conditioned eyeblinks. Brain Res 1122:143-53

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