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

Author:

Pati Sthitapranjya1ORCID,Saba Kamal2ORCID,Salvi Sonali S1,Tiwari Praachi1,Chaudhari Pratik R1,Verma Vijaya3,Mukhopadhyay Sourish1,Kapri Darshana1,Suryavanshi Shital1,Clement James P3,Patel Anant B2,Vaidya Vidita A1ORCID

Affiliation:

1. Department of Biological Sciences, Tata Institute of Fundamental Research, Mumbai, India

2. Centre for Cellular and Molecular Biology, Hyderabad, India

3. Neuroscience Unit, Jawaharlal Nehru Centre for Advanced Scientific Research, Bengaluru, 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.

Funder

Tata Institute of Fundamental Research

Publisher

eLife Sciences Publications, Ltd

Subject

General Immunology and Microbiology,General Biochemistry, Genetics and Molecular Biology,General Medicine,General Neuroscience

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