Dean, Isabel; (2002) Synaptic inhibition of cerebellar Purkinje cells. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

The axons of Purkinje cells are the only efferent projections of the cerebellar cortex. Synaptic inhibition exerts critical control over Purkinje cell firing activity, and thereby immediately influences cerebellar cortical output. Two inhibitory synaptic inputs to Purkinje cells, arising from basket cells and stellate cells, have been studied extensively, and are well characterised in the literature. In this study, electrophysiological recordings and confocal imaging in cerebellar slices are combined with modelling techniques, to find and characterise two novel inhibitory synaptic inputs to Purkinje cells in neonatal (thirteen - fifteen day-old) rats. The first input is proposed to arise from the Lugaro cell, a rare type of cerebellar interneurone that is excited by the monoamine serotonin. The putative Lugaro cell - Purkinje cell synaptic connection displays unusual pharmacology, being recorded under conditions in which all other synaptic inputs to Purkinje cells are blocked. Modelling competitive antagonism of GABAA receptors suggests that this pharmacology results from an unusually long GABA dwell time and / or high GABA concentration in the synaptic cleft. The pharmacology may reflect the immature state of the synaptic connections, for, similarly to other synapses of the cerebellar cortex, the physiology and morphology of the novel synapses are likely to undergo marked developmental changes following the age studied. The input is subject to strong GABAA receptor-mediated presynaptic modulation, resulting in a dynamic range from almost 0 % to 90 % release probability. It is suggested that the presynaptic modulation renders the input sensitive to background GABA, and might allow Lugaro cell - Purkinje cell synapses to become active when the activity of basket cells and stellate cells is reduced. The second synaptic connection examined in this work is suggested to arise between Purkinje cells themselves. There has long been anatomical evidence for a synapse between Purkinje cells, but no functional connection has yet been directly demonstrated. Simultaneous recordings of pairs of Purkinje cells, and subsequent statistical analysis of their synaptic activities, are presented to give evidence of such a connection. Finally, possible implications of the proposed novel synaptic connections, which have as yet been observed only at this immature stage of cerebellar synaptic development, are considered in terms of the function of the cerebellum.

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