Purkinje cell neurotransmission patterns cerebellar basket cells into zonal modules defined by distinct pinceau sizes.

Joy Zhou,Amanda M Brown,Tao Lin,Elizabeth P Lackey,Marife Arancillo,Roy V Sillitoe

doi:10.7554/elife.55569

Abstract

Ramón y Cajal proclaimed the neuron doctrine based on circuit features he exemplified using cerebellar basket cell projections. Basket cells form dense inhibitory plexuses that wrap Purkinje cell somata and terminate as pinceaux at the initial segment of axons. Here, we demonstrate that HCN1, Kv1.1, PSD95 and GAD67 unexpectedly mark patterns of basket cell pinceaux that map onto Purkinje cell functional zones. Using cell-specific genetic tracing with an Ascl1CreERT2 mouse conditional allele, we reveal that basket cell zones comprise different sizes of pinceaux. We tested whether Purkinje cells instruct the assembly of inhibitory projections into zones, as they do for excitatory afferents. Genetically silencing Purkinje cell neurotransmission blocks the formation of sharp Purkinje cell zones and disrupts excitatory axon patterning. The distribution of pinceaux into size-specific zones is eliminated without Purkinje cell GABAergic output. Our data uncover the cellular and molecular diversity of a foundational synapse that revolutionized neuroscience.

Highlights

Studies of the cerebellar basket cell, first by Camillo Golgi and by Santiago Ramón y Cajal, hold a special place in history
All four cell types project onto the 116 Purkinje cells, which make up the middle cerebellar cortical layer called the Purkinje cell layer
We identify that hyperpolarization-activated cyclic nucleotide-gated channel 1 (HCN1), Kv1.1, PSD95, and GAD67 are all expressed in basket cell pinceaux and uncover a pattern of zones in the adult cerebellum

Summary

Introduction

Studies of the cerebellar basket cell, first by Camillo Golgi and by Santiago Ramón y Cajal, hold a special place in history. It was Cajal’s discovery that the endings of basket cells terminate upon what would become known as the initial segment of the Purkinje cells that sparked a new era of neuroscience (Cajal, 1911). The electrical and chemical connectivity coefficients of basket cells are strongly represented in the sagittal plane (Rieubland et al, 2014) It is unclear how this functional organization fits into that of the broader cerebellar map with its complex but systematic patterns of topographic connectivity (Apps et al, 2018)

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