Chronic postnatal chemogenetic activation of forebrain excitatory neurons evokes persistent changes in mood behavior

  1. Sthitapranjya Pati  Is a corresponding author
  2. Kamal Saba
  3. Sonali S Salvi
  4. Praachi Tiwari
  5. Pratik R Chaudhari
  6. Vijaya Verma
  7. Sourish Mukhopadhyay
  8. Darshana Kapri
  9. Shital Suryavanshi
  10. James P Clement
  11. Anant B Patel
  12. Vidita A Vaidya  Is a corresponding author
  1. Tata Institute of Fundamental Research, India
  2. Centre for Cellular and Molecular Biology, India
  3. Jawaharlal Nehru Centre for Advanced Scientific Research, India

Abstract

Early adversity is a risk factor for the development of adult psychopathology. Common across multiple rodent models of early adversity is increased signaling via forebrain Gq-coupled neurotransmitter receptors. We addressed whether enhanced Gq-mediated signaling in forebrain excitatory neurons during postnatal life can evoke persistent mood-related behavioral changes. Excitatory hM3Dq DREADD-mediated chemogenetic activation of forebrain excitatory neurons during postnatal life (P2-14), but not in juvenile or adult windows, increased anxiety-, despair-, and schizophrenia-like behavior in adulthood. This was accompanied by an enhanced metabolic rate of cortical and hippocampal glutamatergic and GABAergic neurons. Furthermore, we observed reduced activity and plasticity-associated marker expression, and perturbed excitatory/inhibitory currents in the hippocampus. These results indicate that Gq signaling mediated activation of forebrain excitatory neurons during the critical postnatal window is sufficient to program altered mood-related behavior, as well as functional changes in forebrain glutamate and GABA systems, recapitulating aspects of the consequences of early adversity.

Data availability

All data generated or analysed during are included in the manuscript and supporting files. Source data files have been provided for Figure 2 and Figure 3.

Article and author information

Author details

  1. Sthitapranjya Pati

    Department of Biological Sciences, Tata Institute of Fundamental Research, Mumbai, India
    For correspondence
    sthita.pati@gmail.com
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8598-4376
  2. Kamal Saba

    NMR spectroscopy and microimaging, Centre for Cellular and Molecular Biology, Hyderabad, India
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1729-9961
  3. Sonali S Salvi

    Department of Biological Sciences, Tata Institute of Fundamental Research, Mumbai, India
    Competing interests
    No competing interests declared.
  4. Praachi Tiwari

    Department of Biological Sciences, Tata Institute of Fundamental Research, Mumbai, India
    Competing interests
    No competing interests declared.
  5. Pratik R Chaudhari

    Department of Biological Sciences, Tata Institute of Fundamental Research, Mumbai, India
    Competing interests
    No competing interests declared.
  6. Vijaya Verma

    Neuroscience Unit, Jawaharlal Nehru Centre for Advanced Scientific Research, Bengaluru, India
    Competing interests
    No competing interests declared.
  7. Sourish Mukhopadhyay

    Department of Biological Sciences, Tata Institute of Fundamental Research, Mumbai, India
    Competing interests
    No competing interests declared.
  8. Darshana Kapri

    Department of Biological Sciences, Tata Institute of Fundamental Research, Mumbai, India
    Competing interests
    No competing interests declared.
  9. Shital Suryavanshi

    Department of Biological Sciences, Tata Institute of Fundamental Research, Mumbai, India
    Competing interests
    No competing interests declared.
  10. James P Clement

    Neuroscience Unit, Jawaharlal Nehru Centre for Advanced Scientific Research, Bengaluru, India
    Competing interests
    No competing interests declared.
  11. Anant B Patel

    CSIR, Centre for Cellular and Molecular Biology, Hyderabad, India
    Competing interests
    No competing interests declared.
  12. Vidita A Vaidya

    Department of Biological Sciences, Tata Institute of Fundamental Research, Mumbai, India
    For correspondence
    vvaidya@tifr.res.in
    Competing interests
    Vidita A Vaidya, Reviewing editor, eLife.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-3907-8580

Funding

Tata Institute of Fundamental Research (RTI4003)

  • Vidita A Vaidya

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

Ethics

Animal experimentation: All animal experiments were carried out in strict accordance with the guideline of the Committee for the Purpose of Control and Supervision of Experiments on Animals (CPCSEA), Government of India. Experiments and use of animals were approved by the institutional ethics committees of the Tata Institute of Fundamental Research, Mumbai, India (TIFR/IAEC/2017-2; 56/GO/ReBi/S/99/CPCSEA); Jawaharlal Nehru Centre for Advanced Scientific Research, Bengaluru, India ( JPC001, JPC005; 201/GO/Re/S/2000/CPCSEA); and Centre for Cellular and Molecular Biology, Hyderabad, India (IAEC 32/2018; 20/GO/RBi/S/99/CPCSEA). Care was taken across all experiments to minimize animal suffering and restrict the number of animals used.

Reviewing Editor

  1. Joseph F Cheer, University of Maryland School of Medicine, United States

Publication history

  1. Received: February 19, 2020
  2. Accepted: September 18, 2020
  3. Accepted Manuscript published: September 21, 2020 (version 1)
  4. Version of Record published: November 9, 2020 (version 2)

Copyright

© 2020, Pati 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. Sthitapranjya Pati
  2. Kamal Saba
  3. Sonali S Salvi
  4. Praachi Tiwari
  5. Pratik R Chaudhari
  6. Vijaya Verma
  7. Sourish Mukhopadhyay
  8. Darshana Kapri
  9. Shital Suryavanshi
  10. James P Clement
  11. Anant B Patel
  12. Vidita A Vaidya
(2020)
Chronic postnatal chemogenetic activation of forebrain excitatory neurons evokes persistent changes in mood behavior
eLife 9:e56171.
https://doi.org/10.7554/eLife.56171

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