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Behavioral role of PACAP reflects its selective distribution in glutamatergic and GABAergic neuronal subpopulations

  1. Limei Zhang  Is a corresponding author
  2. Vito S Hernandez
  3. Charles R Gerfen
  4. Sunny Z Jiang
  5. Lilian Zavala
  6. Rafael A Barrio
  7. Lee E Eiden  Is a corresponding author
  1. National Autonomous University of Mexico, Mexico
  2. National Institute of Mental Health, United States
  3. National Institutes of Health, United States
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Cite this article as: eLife 2021;10:e61718 doi: 10.7554/eLife.61718

Abstract

The neuropeptide PACAP, acting as a co-transmitter, increases neuronal excitability, which may enhance anxiety and arousal associated with threat conveyed by multiple sensory modalities. The distribution of neurons expressing PACAP and its receptor, PAC1, throughout the mouse nervous system was determined, in register with expression of glutamatergic and GABAergic neuronal markers, to develop a coherent chemoanatomical picture of PACAP role in brain motor responses to sensory input. A circuit role for PACAP was tested by observing fos activation of brain neurons after olfactory threat cue in wild type and PACAP knockout mice. Neuronal activation, and behavioral response, were blunted in PACAP knock-out mice, accompanied by sharply down-regulated vesicular transporter expression in both GABAergic and glutamatergic neurons expressing PACAP and its receptor. This report signals a new perspective on the role of neuropeptide signaling in supporting excitatory and inhibitory neurotransmission in the nervous system within functionally coherent polysynaptic circuits.

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Author details

  1. Limei Zhang

    Medicine-Physiology, National Autonomous University of Mexico, Mexico City, Mexico
    For correspondence
    limei@unam.mx
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-7422-5136

  2. Vito S Hernandez

    Medicine-Physiology, National Autonomous University of Mexico, Mexico City, Mexico
    Competing interests
    The authors declare that no competing interests exist.

  3. Charles R Gerfen

    Laboratory of Systems Neuroscience, National Institute of Mental Health, Bethesda, United States
    Competing interests
    The authors declare that no competing interests exist.

  4. Sunny Z Jiang

    Section on Molecular Neuroscience, National Institute of Mental Health, National Institutes of Health, Bethesda, United States
    Competing interests
    The authors declare that no competing interests exist.

  5. Lilian Zavala

    Medicine-Physiology, National Autonomous University of Mexico, Mexico City, Mexico
    Competing interests
    The authors declare that no competing interests exist.

  6. Rafael A Barrio

    Department of complex systems, Institute of Physics, National Autonomous University of Mexico, Mexico City, Mexico
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-0987-0785

  7. Lee E Eiden

    Section on Molecular Neuroscience, National Institute of Mental Health, National Institutes of Health, Bethesda, United States
    For correspondence
    eidenl@nih.gov
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-7524-944X

Funding

Consejo Nacional de Ciencia y Tecnología (CB238744)

  • Limei Zhang

National Institute of Mental Health (NIMH-IRP-1ZIAMH002386)

  • Lee E Eiden

Universidad Nacional Autónoma de México (IN216918)

  • Limei Zhang

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 experiments were approved by the NIMH Institutional Animal Care and Use Committee (ACUC, LCMR-08) and conducted in accordance with the NIH guidelines.

Reviewing Editor

  1. Rebecca Shansky, Northeastern University, United States

Publication history

  1. Received: August 5, 2020
  2. Accepted: January 18, 2021
  3. Accepted Manuscript published: January 19, 2021 (version 1)
  4. Version of Record published: February 10, 2021 (version 2)

Copyright

This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.

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