Ian Duguid

30 septembre 2016

SEMINAIRE TUTORE

Centre for Integrative Physiology, School of Biomedical Sciences, University of Edinburgh, UK

Dendritic excitation-inhibition balance shapes cerebellar output during motor behavior

invité par le PhD program


Abstract : Feedforward excitatory and inhibitory circuits regulate cerebellar output, but how these circuits interact to shape the somatodendritic excitability of Purkinje cells during motor behaviour remains unresolved. Here we performed dendritic and somatic patch-clamp recordings in vivo with optogenetic silencing of interneurons to investigate how dendritic excitation and inhibition interact to generate bidirectional (i.e. increased or decreased) Purkinje cell output during self-paced locomotion. We found that granule cells generated a sustained depolarization of Purkinje cell dendrites during movement, which was counterbalanced by variable levels of feedforward inhibition from local interneurons. Subtle differences in the dendritic excitation-inhibition balance generated robust, bidirectional changes in simple spike (SSp) output. Disrupting this balance by selectively silencing molecular layer interneurons resulted in unidirectional firing rate changes, increased SSp regularity and disrupted locomotor behaviour. Our findings provide a mechanistic understanding of how feedforward excitatory and inhibitory circuits generate bidirectional modulation of Purkinje cell output during self-paced locomotion.

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