Cerebellar cortical inhibition and classical eyeblink conditioning

doi:10.1073/pnas.032655399

Cerebellar cortical inhibition and classical eyeblink conditioning

Neuroscience Program, University of Southern California, Los Angeles, CA 90089-2520

Contributed by Richard F. Thompson

Abstract

The cerebellum is considered a brain structure in which memories for learned motor responses (e.g., conditioned eyeblink responses) are stored. Within the cerebellum, however, the relative importance of the cortex and the deep nuclei in motor learning/memory is not entirely clear. In this study, we show that the cerebellar cortex exerts both basal and stimulus-activated inhibition to the deep nuclei. Sequential application of a γ-aminobutyric acid type A receptor (GABA_AR) agonist and a noncompetitive GABA_AR antagonist allows selective blockade of stimulus-activated inhibition. By using the same sequential agonist and antagonist methods in behaving animals, we demonstrate that the conditioned response (CR) expression and timing are completely dissociable and involve different inhibitory inputs; although the basal inhibition modulates CR expression, the conditioned stimulus-activated inhibition is required for the proper timing of the CR. In addition, complete blockade of cerebellar deep nuclear GABA_ARs prevents CR acquisition. Together, these results suggest that different aspects of the memories for eyeblink CRs are encoded in the cerebellar cortex and the cerebellar deep nuclei.

learning‖memory‖cerebellar deep nuclei‖cerebellar cortex‖ γ-aminobutyric acid

Footnotes

↵ * Present address: Keck Center for Integrative Neuroscience, University of California, San Francisco, CA 94143.
↵ † Present address: Department of Cellular and Molecular Pharmacology, University of California, San Francisco, CA 94143.
↵ ‡ Present address: Department of Psychology, Yale University, 2 Hillhouse Avenue, New Haven, CT 06520-8205.
↵ § To whom reprint requests should be addressed. E-mail: thompson{at}neuro.usc.edu.
Abbreviations:

CS,

conditioned stimulus;

US,

unconditioned stimulus;

CR,

conditioned response;

UR,

unconditioned response;

mf,

mossy fiber;

cf,

climbing fiber;

PC,

Purkinje cell;

DNN,

cerebellar deep nuclear neuron;

LTD,

long-term depression;

AP,

action potential;

EPSP,

excitatory postsynaptic potential;

IPSP,

inhibitory postsynaptic potential;

IPSC,

inhibitory postsynaptic current;

ACSF,

artificial cerebrospinal fluid;

GABA,

γ-aminobutyric acid;

GABAAR,

GABA type A receptor;

PTX,

picrotoxin