title: Dendritic excitation-inhibition balance shapes cerebellar output during motor behaviour.
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 perform dendritic and somatic patch-clamp recordings in vivo combined with optogenetic silencing of interneurons to investigate how dendritic excitation and inhibition generates bidirectional (that is, increased or decreased) Purkinje cell output during self-paced locomotion. We find that granule cells generate a sustained depolarization of Purkinje cell dendrites during movement, which is counterbalanced by variable levels of feedforward inhibition from local interneurons. Subtle differences in the dendritic excitation-inhibition balance generate robust, bidirectional changes in simple spike (SSp) output. Disrupting this balance by selectively silencing molecular layer interneurons results 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 shape Purkinje cell output during motor behaviour.
authors.affiliation: Centre for Integrative Physiology and Patrick Wild Centre, University of Edinburgh, Edinburgh Medical School: Biomedical Sciences, Hugh Robson Building, George Square, Edinburgh EH8 9XD, UK.|Institute of Experimental Medicine, Hungarian Academy of Sciences, H-1083 Budapest, Hungary.
authors.forename: Marta
authors.initials: M
authors.lastname: Jelitai
authors.affiliation: Centre for Integrative Physiology and Patrick Wild Centre, University of Edinburgh, Edinburgh Medical School: Biomedical Sciences, Hugh Robson Building, George Square, Edinburgh EH8 9XD, UK.|Institute for Adaptive and Neural Computation, School of Informatics, University of Edinburgh, Edinburgh EH8 9AB, UK.|Neuroinformatics Doctoral Training Centre, School of Informatics, University of Edinburgh, Edinburgh EH8 9AB, UK.
authors.forename: Paolo
authors.initials: P
authors.lastname: Puggioni
authors.affiliation: Department of Pharmacology, Jikei University School of Medicine, Tokyo 105-8461, Japan.
authors.forename: Taro
authors.initials: T
authors.lastname: Ishikawa
authors.affiliation: Centre for Integrative Physiology and Patrick Wild Centre, University of Edinburgh, Edinburgh Medical School: Biomedical Sciences, Hugh Robson Building, George Square, Edinburgh EH8 9XD, UK.
authors.forename: Arianna
authors.initials: A
authors.lastname: Rinaldi
authors.affiliation: Centre for Integrative Physiology and Patrick Wild Centre, University of Edinburgh, Edinburgh Medical School: Biomedical Sciences, Hugh Robson Building, George Square, Edinburgh EH8 9XD, UK.
authors.forename: Ian
authors.initials: I
authors.lastname: Duguid
mesh_terms: D000818:Animals; D002531:Cerebellum / Q000166:cytology / Q000502:physiology; D003712:Dendrites / Q000502:physiology*; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D007395:Interneurons / Q000502:physiology; D008124:Locomotion / Q000502:physiology*; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000502:physiology*; D009433:Neural Inhibition / Q000502:physiology*; D062308:Optogenetics; D018408:Patch-Clamp Techniques; D011689:Purkinje Cells / Q000502:physiology*