神经科学
谷氨酸的
海马结构
海马体
FOSB公司
慢性应激
心情
分子神经科学
心理学
生物
转录因子
谷氨酸受体
基因
精神科
遗传学
受体
作者
Andrew L. Eagle,Claire Manning,Elizabeth Williams,Ryan M. Bastle,Paula A. Gajewski,Amber Garrison,Alexis J. Wirtz,Seda Akguen,Katie Brandel-Ankrapp,Wilson O. Endege,Frederick M. Boyce,Yoshinori N. Ohnishi,Michelle S. Mazei‐Robison,Ian Maze,Rachel L. Neve,Alfred J. Robison
标识
DOI:10.1038/s41467-020-17825-x
摘要
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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