The Cerebello-Olivary Feedback System

University dissertation from Department of Experimental Medical Science

Abstract: The pathway from the deep cerebellar nuclei to the inferior olive, the nucleo-olivary pathway, is known to be inhibitory. The physiological and temporal properties, as well as the localisation, of the nucleo-olivary pathway were characterised in the decerebrate ferret. The results were used to investigate the suggestion that the nucleo-olivary pathway is part of a negative feedback system for the regulation of spontaneous Purkinje cell activity. This hypothesis was proposed because output from the inferior olive, via the climbing fibres, is known to depress Purkinje cell activity. The feedback hypothesis was tested both by blocking and by stimulating the nucleo-olivary pathway. Blocking was followed by an increased climbing fibre activity and a rapid decrease of Purkinje cell background activity. Stimulation of the nucleo-olivary pathway caused the reverse effect. The results from the initial investigation were also applied in behavioural studies to investigate the pathway for the unconditioned stimulus signal in classical conditioning of the eyeblink reflex. It has been suggested that the climbing fibres transmit the unconditioned stimulus signal to the cerebellum. Repeated presentations of the conditioned stimulus on its own leads to extinction of the conditioned response. If the unconditioned stimulus signal is transmitted to the cerebellum via the inferior olive?climbing fibre system, then stimulation of the nucleo-olivary pathway just prior to the unconditioned stimulus, in a trained animal, should lead to extinction. As the nucleo-olivary stimulation was introduced into the conditioning paradigm the conditioned responses were gradually extinguished, thus confirming the prediction.

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