Impaired classical eyeblink conditioning in cerebellar-lesioned and Purkinje cell degeneration (pcd) mutant mice

Lu Chen, Shaowen Bao, Jon M. Lockard, Jeansok J. Kim, Richard F. Thompson

Research output: Contribution to journalArticlepeer-review

191 Scopus citations

Abstract

Converging lines of evidence from rabbits, rats, and humans argue for the crucial involvement of the cerebellum in classical conditioning of the eyeblink/nictitating membrane response in mammals. For example, selective lesions (permanent or reversible) of the cerebellum block both acquisition and retention of eyeblink conditioning. Correspondingly, electrophysiological and brain-imaging studies indicate learning-related plasticity in the cerebellum. The involvement of the cerebellum in eyeblink conditioning is also supported by stimulation studies showing that direct stimulation of the two major afferents to the cerebellum (the mossy fibers emanating from the pontine nucleus and climbing fibers originating from the inferior olive) can substitute for the peripheral conditioned stimulus (OS) and unconditioned stimulus (US), respectively, to yield normal behavioral learning. In the present study, we examined the relative contribution of the cerebellar cortex versus deep nuclei (specifically the interpositus nucleus) in eyeblink learning by using mutant mice deficient of Purkinje cells, the exclusive output neurons of the cerebellar cortex. We report that Purkinje cell degeneration (pcd) mice exhibit a profound impairment in the acquisition of delay eyeblink conditioning in comparison with their wild-type littermates. Nevertheless, the pcd animals did acquire a subnormal level of conditioned eyeblink responses. In contrast, wild-type mice with lesions of the interpositus nucleus were completely unable to learn the conditioned eyeblink response. These results suggest that both cerebellar cortex and deep nuclei are important for normal eyeblink conditioning.

Original languageEnglish (US)
Pages (from-to)2829-2838
Number of pages10
JournalJournal of Neuroscience
Volume16
Issue number8
DOIs
StatePublished - Apr 15 1996
Externally publishedYes

Keywords

  • Purkinje cells
  • cerebellum
  • eyeblink conditioning
  • interpositus nucleus
  • learning
  • long-term depression
  • memory
  • mutant mice

ASJC Scopus subject areas

  • Neuroscience(all)

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