Purkinje cell neurotransmission patterns cerebellar basket cells into zonal modules defined by distinct pinceau sizes
- Baylor College of Medicine, United States
- Texas Children's Hospital, United States
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.
Data availability
All data generated or analyzed during this study are included in the manuscript and supporting files. Source data files have been provided for Figures 2, 4, 6, 7, and 8.
Article and author information
Author details
Funding
Baylor College of Medicine
- Joy Zhou
- Amanda M Brown
- Elizabeth P Lackey
- Marife Arancillo
- Tao Lin
- Roy V Sillitoe
Texas Children's Hospital
- Joy Zhou
- Amanda M Brown
- Elizabeth P Lackey
- Marife Arancillo
- Tao Lin
- Roy V Sillitoe
Bachmann-Strauss Dystonia and Parkinson Foundation
- Roy V Sillitoe
National Center for Research Resources (C06RR029965)
- Roy V Sillitoe
National Institute of Neurological Disorders and Stroke (R01NS089664,R01NS100874)
- Roy V Sillitoe
National Ataxia Foundation (Postdoctoral Award)
- Marife Arancillo
National Institutes of Health (F31NS101891)
- Amanda M Brown
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All animals were housed in an AALAS-certified facility on a 14hr light cycle. Husbandry, housing, euthanasia, and experimental guidelines were reviewed and approved by the Institutional Animal Care and Use Committee (IACUC) of Baylor College of Medicine (protocol number: AN-5996).
Copyright
© 2020, Zhou et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Purkinje cell neurotransmission patterns cerebellar basket cells into zonal modules defined by distinct pinceau sizes
eLife 9:e55569.
https://doi.org/10.7554/eLife.55569
