Neurons of the cerebellar nuclei are spontaneously active neurons that integrate excitatory input from mossy fibers and inhibitory input from Purkinje neurons to generate the output of the cerebellum. In real time, cerebellar output corrects errors and facilitates learned, coordinated movements, raising the question of how inhibition, excitation, and intrinsic firing interact to regulate the firing patterns of cerebellar nuclear cells. The present proposal is directed toward testing the idea that nuclear cells'response to Purkinje-mediated inhibition varies according to the correction or regulation produced by the cerebellum at any time. In particular, the degree of inhibitory synchrony may dictate cerebellar output in a task-dependent manner. Experiments will be performed both in vitro and in vivo, in normal and mutant mice and in zebrafish. Voltage-clamp, current-clamp, and extracellular electrophysiological recordings will be used to test the changes in correlation of Purkinje and nuclear cell activity during practiced motor behaviors and during errors, the interaction of excitatory with inhibitory inputs, and the changes in Purkinje synchrony and nuclear cell output during learning.

Public Health Relevance

The cerebellum regulates movements and various aspects of cognitive function, and its dysfunction is associated with ataxia, dystonia, dyslexia, and autism. Information about sensory signals are received by Purkinje neurons in the cerebellum, which then modify the information and send it to neurons in the cerebellar nuclei, which further process the information and then send it to parts of the brain that control the timing and sequencing of behaviors. In the present application, we propose to study how signals are transmitted and transformed as they go from Purkinje neurons to neurons in the cerebellar nuclei, and what changes arise under pathological conditions.

Agency
National Institute of Health (NIH)
Type
Method to Extend Research in Time (MERIT) Award (R37)
Project #
2R37NS039395-14A1
Application #
8775581
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Talley, Edmund M
Project Start
Project End
Budget Start
Budget End
Support Year
14
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Northwestern University at Chicago
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
City
Evanston
State
IL
Country
United States
Zip Code
60201