Circuit-specific Hippocampal ΔFosB Underlies Resilience to Stress-induced Social Avoidance

Overview

Journal Nat Commun

Specialty Biology

Date 2020 Sep 9

PMID 32901027

Citations 28

Authors

Andrew L Eagle

Claire E Manning

Elizabeth S Williams

Ryan M Bastle

Paula A Gajewski

Amber Garrison

Alexis J Wirtz

Seda Akguen

Katie Brandel-Ankrapp

Wilson Endege

Frederick M Boyce

Yoshinori N Ohnishi

Michelle Mazei-Robison

Ian Maze

Rachel L Neve

Alfred J Robison

Affiliations

Soon will be listed here.

Abstract

Chronic 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.

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