Behavioral role of PACAP reflects its selective distribution in glutamatergic and GABAergic neuronal subpopulations
- National Autonomous University of Mexico, Mexico
- National Institute of Mental Health, United States
- National Institutes of Health, United States
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.
Data availability
All data generated or analysed during this study are included in the manuscript and supporting files. Source data files have been provided for Figures.
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Allen Mouse Brain Atlashttp://help.brain-map.org/display/mousebrain/In+Situ+Hybridization+%28ISH%29+Data.
Article and author information
Author details
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.
Reviewing Editor
- Rebecca Shansky, Northeastern University, United States
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.
Version history
- Received: August 5, 2020
- Accepted: January 18, 2021
- Accepted Manuscript published: January 19, 2021 (version 1)
- 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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Behavioral role of PACAP reflects its selective distribution in glutamatergic and GABAergic neuronal subpopulations
eLife 10:e61718.
https://doi.org/10.7554/eLife.61718
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