Cerebellar Control of Classical Conditioning

Abstract: It has previously been shown that the cerebellum is critical for classical conditioning. The experiments presented in this thesis aimed to study how the cerebellum controls conditioned eyeblink responses (CRs) and specifically the efferent path from the cerebellar cortex to the muscles. Ferrets, decerebrated rostral to the superior colliculus and the red nucleus, were trained in a classical conditioning paradigm. The conditioned stimulus (CS) was a train of electrical stimuli applied to the forelimb and the unconditioned stimulus (US) was a train of electrical stimuli to the periorbital region. The EMG was recorded from the orbicularis oculi muscle. The animal received CS-US trials (ITI 20-60s) until eyeblink CRs occurred on virtually every trial. Cerebellar learning theories suggest a critical role for the climbing fibres in learning of a CR. By recording from Purkinje cells with short latency climbing fibre input from the periorbital area, we showed that a subpopulation of Purkinje cells in the C3 zone responded to the CS with a suppression of simple spike firing only in trained animals. The suppression was more pronounced during the later parts of the CS period, and in a few cells the suppression was preceded by a short period of increased simple spike firing. This is in agreement with the Marr-Albus theory of motor learning in the cerebellum. The inferior olive is the only source of climbing fibre input to the cerebellar cortex and regulating the transmission through the olive would be an efficient way of controlling the learning of a CR. We showed that cerebellar output during performance of a CR inhibits the inferior olive, most likely via the GABAergic nucleo-olivary pathway. This provides negative feed-back information to the olive thereby regulating the amplitude of the CR. Reports have shown that CRs can recover after unilateral cerebellar lesions, but if the output from the cerebellum was bilateral the nonlesioned cerebellar side could produce the recovered CRs. We showed that there is a bilateral control of the eyeblink from each cerebellar hemisphere. It is possible that the bilateral output is not involved in expressing CRs, but our results clearly showed that this bilateral pathway exerts a marked control of contralateral eyeblink CRs. It is also suggested that the cerebellar control of the contralateral orbicularis oculi muscle is mediated via premotor neurones that are specifically involved in the CR and not the UR. These results make the reports of recovery after unilateral cerbellar lesions inconclusive. A detailed knowledge of how the orbicularis oculi muscle is activated during the execution of a CR is a critical step to understanding the underlying neural mechanisms involved in the control of the CR. We showed that the eyeblink CR consists of two components, CR1 and CR2, which most likely originate either as a direct central command from the cerebellum or in the output pathway before the output reaches the facial nucleus.