1. Neuroscience
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Modular output circuits of the fastigial nucleus for diverse motor and nonmotor functions of the cerebellar vermis

  1. Hirofumi Fujita  Is a corresponding author
  2. Takashi Kodama
  3. Sascha du Lac  Is a corresponding author
  1. Johns Hopkins University, United States
  2. Johns Hopkins Medical Institute, United States
Research Article
  • Cited 23
  • Views 3,194
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Cite this article as: eLife 2020;9:e58613 doi: 10.7554/eLife.58613

Abstract

The cerebellar vermis, long associated with axial motor control, has been implicated in a surprising range of neuropsychiatric disorders and cognitive and affective functions. Remarkably little is known, however, about the specific cell types and neural circuits responsible for these diverse functions. Here, using single-cell gene expression profiling and anatomical circuit analyses of vermis output neurons in the mouse fastigial (medial cerebellar) nucleus, we identify five major classes of glutamatergic projection neurons distinguished by gene expression, morphology, distribution, and input-output connectivity. Each fastigial cell type is connected with a specific set of Purkinje cells and inferior olive neurons and in turn innervates a distinct collection of downstream targets. Transsynaptic tracing indicates extensive disynaptic links with cognitive, affective, and motor forebrain circuits. These results indicate that diverse cerebellar vermis functions could be mediated by modular synaptic connections of distinct fastigial cell types with posturomotor, oromotor, positional-autonomic, orienting, and vigilance circuits.

Data availability

All data analyzed during this study are included in the manuscript and supporting files.

Article and author information

Author details

  1. Hirofumi Fujita

    Otolaryngology-HNS, Johns Hopkins University, Baltimore, United States
    For correspondence
    hirofumi@jhmi.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9630-2756
  2. Takashi Kodama

    Otolaryngolgy, Johns Hopkins University, Baltimore, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-3110-979X
  3. Sascha du Lac

    Otolaryngology, Neuroscience, Neurology, Johns Hopkins Medical Institute, Baltimore, United States
    For correspondence
    sascha@jhmi.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-4669-3191

Funding

National Institute of Neurological Disorders and Stroke (NS095232)

  • Sascha du Lac

National Institute of Neurological Disorders and Stroke (NS105039)

  • Sascha du Lac

Japan Society for the Promotion of Science (26-585)

  • Hirofumi Fujita

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: All procedures conformed to NIH guidelines and were approved by the Johns Hopkins University Animal Care and Use Committee (M014M28 and M016M464) and Salk Institute Animal Care and Use Committee (11-00024).

Reviewing Editor

  1. Harry T Orr, University of Minnesota, United States

Publication history

  1. Received: May 5, 2020
  2. Accepted: July 7, 2020
  3. Accepted Manuscript published: July 8, 2020 (version 1)
  4. Version of Record published: August 19, 2020 (version 2)

Copyright

© 2020, Fujita 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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