Basket to Purkinje Cell Inhibitory Ephaptic Coupling Is Abolished in Episodic Ataxia Type 1

Author:

Martin Henry G. S.1,Kullmann Dimitri M.1

Affiliation:

1. Department of Clinical and Experimental Epilepsy, UCL Queen Square Institute of Neurology, University College London, London WC1N 3BG, UK

Abstract

Dominantly inherited missense mutations of the KCNA1 gene, which encodes the KV1.1 potassium channel subunit, cause Episodic Ataxia type 1 (EA1). Although the cerebellar incoordination is thought to arise from abnormal Purkinje cell output, the underlying functional deficit remains unclear. Here we examine synaptic and non-synaptic inhibition of Purkinje cells by cerebellar basket cells in an adult mouse model of EA1. The synaptic function of basket cell terminals was unaffected, despite their intense enrichment for KV1.1-containing channels. In turn, the phase response curve quantifying the influence of basket cell input on Purkine cell output was maintained. However, ultra-fast non-synaptic ephaptic coupling, which occurs in the cerebellar ‘pinceau’ formation surrounding the axon initial segment of Purkinje cells, was profoundly reduced in EA1 mice in comparison with their wild type littermates. The altered temporal profile of basket cell inhibition of Purkinje cells underlines the importance of Kv1.1 channels for this form of signalling, and may contribute to the clinical phenotype of EA1.

Funder

Medical Research Council

Wellcome Trust

Publisher

MDPI AG

Subject

General Medicine

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