Cerebellar circuits and synaptic mechanisms involved in classical eyeblink conditioning.

There is increasing evidence that, in addition to its major functional role in the regulation of fine motor control, the cerebellum is involved in other important functions, such as sensory-motor learning and memory. Classical conditioning of the eyeblink or nictitating membrane response (and other discrete behavioral responses) is a form of sensory-motor learning that depends crucially upon the cerebellum. Within the cerebellum, however, the relative importance of the cerebellar cortex and the deep cerebellar nuclei in eyeblink conditioning is unclear and disputed. Recent studies employing various mutant mice provide an effective approach to resolving this controversy. Eyeblink conditioning in spontaneous mutant mice deficit in Purkinje cells, the exclusive output neurons of the cerebellar cortex, indicate that both the cerebellar cortex and the interpositus nucleus are important. Furthermore, studies involving gene knockout mice suggest that long-term depression, a process of synaptic plasticity occurring in Purkinje cells, might be involved in eyeblink conditioning.