1. Neuroscience

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
https://doi.org/10.7554/eLife.54302
Share this article
Cite this article
  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
  2. Download BibTeX
  3. Download .RIS

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.

Metrics

  • 4,131
    views
  • 600
    downloads
  • 72
    citations

Views, downloads and citations are aggregated across all versions of this paper published by eLife.

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)

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

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

  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

Share this article

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

Categories and tags

Research organism

Further reading

    1. Cell Biology
    2. Neuroscience

    Translational regulation enhances distinction of cell types in the nervous system

    Toshiharu Ichinose, Shu Kondo ... Hiromu Tanimoto
    Research Article

    Multicellular organisms are composed of specialized cell types with distinct proteomes. While recent advances in single-cell transcriptome analyses have revealed differential expression of mRNAs, cellular diversity in translational profiles remains underinvestigated. By performing RNA-seq and Ribo-seq in genetically defined cells in the Drosophila brain, we here revealed substantial post-transcriptional regulations that augment the cell-type distinctions at the level of protein expression. Specifically, we found that translational efficiency of proteins fundamental to neuronal functions, such as ion channels and neurotransmitter receptors, was maintained low in glia, leading to their preferential translation in neurons. Notably, distribution of ribosome footprints on these mRNAs exhibited a remarkable bias toward the 5′ leaders in glia. Using transgenic reporter strains, we provide evidence that the small upstream open-reading frames in the 5’ leader confer selective translational suppression in glia. Overall, these findings underscore the profound impact of translational regulation in shaping the proteomics for cell-type distinction and provide new insights into the molecular mechanisms driving cell-type diversity.

    1. Neuroscience

    Differential functions of the dorsal and intermediate regions of the hippocampus for optimal goal-directed navigation in VR space

    Hyeri Hwang, Seung-Woo Jin, Inah Lee
    Research Article

    Goal-directed navigation requires the hippocampus to process spatial information in a value-dependent manner, but its underlying mechanism needs to be better understood. Here, we investigated whether the dorsal (dHP) and intermediate (iHP) regions of the hippocampus differentially function in processing place and its associated value information. Rats were trained in a place-preference task involving reward zones with different values in a visually rich virtual reality environment where two-dimensional navigation was possible. Rats learned to use distal visual scenes effectively to navigate to the reward zone associated with a higher reward. Inactivation of both dHP and iHP with muscimol altered the efficiency and precision of wayfinding behavior, but iHP inactivation induced more severe damage, including impaired place preference. Our findings suggest that the iHP is more critical for value-dependent navigation toward higher-value goal locations.

    1. Neuroscience

    Neural Plasticity: Restoring cerebellar-dependent learning

    Jessica L Verpeut
    Insight

    Behavioral and pharmaceutical interventions reverse defects associated with increased cerebellar long-term depression in a mouse model of Fragile X syndrome.