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Journal of Neuroscience, Vol 16, 2829-2838, Copyright © 1996 by Society for Neuroscience
Impaired classical eyeblink conditioning in cerebellar-lesioned and Purkinje cell degeneration (pcd) mutant mice
L Chen, S Bao, JM Lockard, JK Kim and RF Thompson
Neuroscience Program, University of Southern California, Los Angeles, 90089-2520, USA.
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 (CS)
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.
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