1. Neuroscience
Download icon

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 17
  • Views 2,354
  • Annotations
Cite this article as: eLife 2020;9:e58613 doi: 10.7554/eLife.58613


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
    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
    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


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.


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)


© 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.


  • 2,354
    Page views
  • 418
  • 17

Article citation count generated by polling the highest count across the following sources: Crossref, PubMed Central, Scopus.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Download citations (links to download the citations from this article in formats compatible with various reference manager tools)

Open citations (links to open the citations from this article in various online reference manager services)

  1. Further reading

Further reading

    1. Neuroscience
    Zachariah Bertels et al.
    Research Article

    Migraine is the third most prevalent disease worldwide but the mechanisms that underlie migraine chronicity are poorly understood. Cytoskeletal flexibility is fundamental to neuronal-plasticity and is dependent on dynamic microtubules. Histone-deacetylase-6 (HDAC6) decreases microtubule dynamics by deacetylating its primary substrate, α-tubulin. We use validated mouse models of migraine to show that HDAC6-inhibition is a promising migraine treatment and reveal an undiscovered cytoarchitectural basis for migraine chronicity. The human migraine trigger, nitroglycerin, produced chronic migraine-associated pain and decreased neurite growth in headache-processing regions, which were reversed by HDAC6 inhibition. Cortical spreading depression (CSD), a physiological correlate of migraine aura, also decreased cortical neurite growth, while HDAC6-inhibitor restored neuronal complexity and decreased CSD. Importantly, a calcitonin gene-related peptide receptor antagonist also restored blunted neuronal complexity induced by nitroglycerin. Our results demonstrate that disruptions in neuronal cytoarchitecture are a feature of chronic migraine, and effective migraine therapies might include agents that restore microtubule/neuronal plasticity.

    1. Cell Biology
    2. Neuroscience
    Stefano Perni, Kurt Beam
    Research Article Updated

    Junctions between the endoplasmic reticulum and plasma membrane that are induced by the neuronal junctophilins are of demonstrated importance, but their molecular architecture is still poorly understood and challenging to address in neurons. This is due to the small size of the junctions and the multiple isoforms of candidate junctional proteins in different brain areas. Using colocalization of tagged proteins expressed in tsA201 cells, and electrophysiology, we compared the interactions of JPH3 and JPH4 with different calcium channels. We found that JPH3 and JPH4 caused junctional accumulation of all the tested high-voltage-activated CaV isoforms, but not a low-voltage-activated CaV. Also, JPH3 and JPH4 noticeably modify CaV2.1 and CaV2.2 inactivation rate. RyR3 moderately colocalized at junctions with JPH4, whereas RyR1 and RyR2 did not. By contrast, RyR1 and RyR3 strongly colocalized with JPH3, and RyR2 moderately. Likely contributing to this difference, JPH3 binds to cytoplasmic domain constructs of RyR1 and RyR3, but not of RyR2.