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Cerebellar Golgi cell models predict dendritic processing and mechanisms of synaptic plasticity

Authors: Stefano Masoli 1, Alessandra Ottaviani 1, Egidio D'Angelo 1,2

Author information: 1 Department of Brain and Behavioral Sciences, University of Pavia, Via Forlanini 6, I-27100, Pavia, Italy, 2 Brain Connectivity Center, IRCCS Mondino Foundation, Via Mondino 2, I-27100, Pavia, Italy,

Corresponding author: Egidio D'Angelo ( dangelo@unipv.it )

Journal: Biorxiv

Download Url: https://www.biorxiv.org/content/10.1101/2020.05.13.093906v1

Citation: Stefano Masoli, Alessandra Ottaviani, Egidio D'Angelo. Cerebellar Golgi cell models predict dendritic processing and mechanisms of synaptic plasticity. Biorxiv 2020.

DOI: https://10.1101/2020.05.13.093906

Licence: the Creative Commons Attribution (CC BY) license  applies for all files. Under this Open Access license anyone may copy, distribute, or reuse the files as long as the authors and the original source are properly cited.

Abstract:
The Golgi cells are the main inhibitory interneurons of the cerebellar granular layer. Although recent works have highlighted the complexity of their dendritic organization and synaptic inputs, the mechanisms through which these neurons integrate complex input patterns remained unknown. Here we have used 8 detailed morphological reconstructions to develop multicompartmental models of Golgi cells, in which Na, Ca, and K channels were distributed along dendrites, soma, axonal initial segment and axon. The models faithfully reproduced a rich pattern of electrophysiological and pharmacological properties and predicted the operating mechanisms of these neurons. Basal dendrites turned out to be more tightly electrically coupled to the axon initial segment than apical dendrites. During synaptic transmission, parallel fibers caused slow Ca-dependent depolarizations in apical dendrites that boosted the axon initial segment encoder and Na-spike backpropagation into basal dendrites, while inhibitory synapses effectively shunted backpropagating currents. This oriented dendritic processing set up a coincidence detector controlling voltage-dependent NMDA receptor unblock in basal dendrites, which, by regulating local calcium influx, may provide the basis for spike-timing dependent plasticity anticipated by theory.
Resources

Electrophysiological data available in the HBP Knowledge Graph and are listed below:

Whole cell patch-clamp recordings of cerebellar Golgi cells
Recordings of cerebellar neuronal firing induced by currents steps
Investigation of spatial distribution of excitation in cerebellar cortical slices
Characterization of spatial distribution of activity in cerebellar cortical slices
Recordings of spontaneous firing of cerebellar interneurons (Golgi cells)

One of the models used in the paper is available at the links reported below. Relevant files are grouped by category: