Chronic postnatal chemogenetic activation of forebrain excitatory neurons evokes persistent changes in mood behavior
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.
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.
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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.
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.
- Joseph F Cheer, University of Maryland School of Medicine, United States
- Received: February 19, 2020
- Accepted: September 18, 2020
- Accepted Manuscript published: September 21, 2020 (version 1)
- Version of Record published: November 9, 2020 (version 2)
© 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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