Cerebellar modulation of synaptic input to freezing-related neurons in the periaqueductal gray

  1. Christopher E Vaaga
  2. Spencer T Brown
  3. Indira M Raman  Is a corresponding author
  1. Northwestern University, United States

Abstract

Innate defensive behaviors, such as freezing, are adaptive for avoiding predation. Freezing-related midbrain regions project to the cerebellum, which is known to regulate rapid sensorimotor integration, raising the question of cerebellar contributions to freezing. Here, we find that neurons of the mouse medial (fastigial) cerebellar nuclei (mCbN), which fire spontaneously with wide dynamic ranges, send glutamatergic projections to the ventrolateral periaqueductal gray (vlPAG), which contains diverse cell types. In freely moving mice, optogenetically stimulating glutamatergic vlPAG neurons that express Chx10 reliably induces freezing. In vlPAG slices, mCbN terminals excite ~20% of neurons positive for Chx10 or GAD2 and ~70% of dopaminergic TH-positive neurons. Stimulating either mCbN afferents or TH neurons augments IPSCs and suppresses EPSCs in Chx10 neurons by activating postsynaptic D2 receptors. The results suggest that mCbN activity regulates dopaminergic modulation of the vlPAG, favoring inhibition of Chx10 neurons. Suppression of cerebellar output may therefore facilitate freezing.

Data availability

All data generated during this study are included in the manuscript and supporting files, and values of individual measurements within a population are included in graphs of data.

The following previously published data sets were used

Article and author information

Author details

  1. Christopher E Vaaga

    Department of Neurobiology, Northwestern University, Evanston, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9777-3808
  2. Spencer T Brown

    Department of Neurobiology, Northwestern University, Evanston, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Indira M Raman

    Department of Neurobiology, Northwestern University, Evanston, United States
    For correspondence
    i-raman@northwestern.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5245-8177

Funding

National Institute of Neurological Disorders and Stroke (F32 NS106720)

  • Christopher E Vaaga

National Institute of Neurological Disorders and Stroke (R37 NS39395)

  • Indira M Raman

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

Reviewing Editor

  1. Julie A Kauer, Stanford University, United States

Ethics

Animal experimentation: All procedures conformed to NIH guidelines and were approved by the Northwestern University Institutional Animal Care and Use Committee, protocol IS00000242 (IMR).

Version history

  1. Received: December 9, 2019
  2. Accepted: March 24, 2020
  3. Accepted Manuscript published: March 24, 2020 (version 1)
  4. Version of Record published: April 3, 2020 (version 2)

Copyright

© 2020, Vaaga 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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  1. Christopher E Vaaga
  2. Spencer T Brown
  3. Indira M Raman
(2020)
Cerebellar modulation of synaptic input to freezing-related neurons in the periaqueductal gray
eLife 9:e54302.
https://doi.org/10.7554/eLife.54302

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https://doi.org/10.7554/eLife.54302