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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\u201314), 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.<\/jats:p>","DOI":"10.7554\/elife.56171","type":"journal-article","created":{"date-parts":[[2020,9,21]],"date-time":"2020-09-21T08:01:07Z","timestamp":1600675267000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.56171","source":"Crossref","is-referenced-by-count":17,"title":["Chronic postnatal chemogenetic activation of forebrain excitatory neurons evokes persistent changes in mood behavior"],"prefix":"10.7554","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8598-4376","authenticated-orcid":true,"given":"Sthitapranjya","family":"Pati","sequence":"first","affiliation":[{"name":"Department of Biological Sciences, Tata Institute of Fundamental Research, 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