Lesions of the inferior olivary complex cause extinction of the classically conditioned eyeblink response

The dentate-interpositus nuclei of the cerebellum are known to be critically involved in the production of the classically conditioned eyeblink response in the rabbit. The rostro-medial portions of the inferior olivary complex (rmIO) project to these nuclei as well as receive projections from the fifth sensory nuclei. Lesions of the rmIO caused a previously classically conditioned eyeblink response to slowly decrease in amplitude and frequency with continued paired conditioned stimulus-unconditioned stimulus (CS-UCS) training in a manner which was identical to extinction of the learned response in control animals. The lesion had no effect on the performance of the unconditioned response. Lesions of the rmIO before training prevented learning from occurring. Lesions of other portions of the IO or of the reticular formation did not specifically affect the learned response. We conclude that the rmIO is critically involved in the learning and maintenance of the classically conditioned eyeblink response. We propose that the rmIO may serve as a pathway for information from the unconditioned stimulus to reach the cerebellum, and as such may in fact be the essential reinforcing or teaching input for the learning of classically conditioned responses. These results support the hypothesis that the cerebellum contains neuronal changes which are a critical portion of the memory trace for the conditioned response.