Circuit-specific hippocampal ΔFosB underlies resilience to stress-induced social avoidance

Author:

Eagle Andrew L.ORCID,Manning Claire E.ORCID,Williams Elizabeth S.ORCID,Bastle Ryan M.,Gajewski Paula A.,Garrison Amber,Wirtz Alexis J.,Akguen Seda,Brandel-Ankrapp Katie,Endege Wilson,Boyce Frederick M.,Ohnishi Yoshinori N.,Mazei-Robison Michelle,Maze Ian,Neve Rachel L.,Robison Alfred J.ORCID

Abstract

AbstractChronic stress is a key risk factor for mood disorders like depression, but the stress-induced changes in brain circuit function and gene expression underlying depression symptoms are not completely understood, hindering development of novel treatments. Because of its projections to brain regions regulating reward and anxiety, the ventral hippocampus is uniquely poised to translate the experience of stress into altered brain function and pathological mood, though the cellular and molecular mechanisms of this process are not fully understood. Here, we use a novel method of circuit-specific gene editing to show that the transcription factor ΔFosB drives projection-specific activity of ventral hippocampus glutamatergic neurons causing behaviorally diverse responses to stress. We establish molecular, cellular, and circuit-level mechanisms for depression- and anxiety-like behavior in response to stress and use circuit-specific gene expression profiling to uncover novel downstream targets as potential sites of therapeutic intervention in depression.

Funder

U.S. Department of Health & Human Services | NIH | National Institute of Mental Health

U.S. Department of Health & Human Services | NIH | National Institute on Drug Abuse

U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke

Brain and Behavior Research Foundation

Publisher

Springer Science and Business Media LLC

Subject

General Physics and Astronomy,General Biochemistry, Genetics and Molecular Biology,General Chemistry

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