Pharmacological analysis of cerebellar contributions to the timing and expression of conditioned eyelid responses

Contradictory results have been reported regarding the effects of cerebellar cortex lesions on the expression of conditioned eyelid responses--either no effect, partial to complete abolition of responses, or disruption of response timing. This uncertainty is increased by debates regarding the region(s) of cerebellar cortex that are involved, by the likelihood that cortex lesions can inadvertently include damage to the interpositus nucleus or other pathways necessary for response expression, and by potential confounds from the degeneration of climbing fibers produced by cerebellar cortex lesions. We have addressed these issues by reversibly blocking cerebellar cortex output via infusion of the GABA antagonist picrotoxin into the interpositus nucleus. After picrotoxin infusion, conditioned responses are spared but their timing is disrupted and their amplitude diminished. In the same animals, conditioned responses were abolished by infusion of the GABA agonist muscimol and were unaffected by infusion of saline vehicle. These results are consistent with the hypothesis that (i) plasticity in the interpositus nucleus contributes to the expression of conditioned responses, as suggested by the responses seen with the cortex disconnected, and (ii) plasticity in the cerebellar cortex also contributes to conditioned response expression, as suggested by disruption of response timing.