Circuit-specific hippocampal ΔFosB underlies resilience to stress-induced social avoidance
| Autor: | Paula A. Gajewski, Seda Akguen, Rachel L. Neve, Frederick M. Boyce, Wilson O. Endege, Claire E. Manning, Ryan M. Bastle, Ian Maze, Andrew L. Eagle, Alfred J. Robison, Michelle S. Mazei-Robison, Amber Garrison, Alexis J. Wirtz, Elizabeth S. Williams, Yoshinori N. Ohnishi, Katie Brandel-Ankrapp |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Male Science General Physics and Astronomy Hippocampus Molecular neuroscience Hippocampal formation Biology Anxiety Neural circuits General Biochemistry Genetics and Molecular Biology Article 03 medical and health sciences Glutamatergic Gene Knockout Techniques Mice 0302 clinical medicine Cellular neuroscience medicine Avoidance Learning Animals Chronic stress Gene Silencing lcsh:Science skin and connective tissue diseases Social Behavior Emotion Mice Knockout Neurons Multidisciplinary Behavior Animal General Chemistry medicine.disease Gene expression profiling Mice Inbred C57BL 030104 developmental biology Mood disorders Diseases of the nervous system lcsh:Q sense organs Neuroscience Proto-Oncogene Proteins c-fos 030217 neurology & neurosurgery Stress Psychological |
| Zdroj: | Nature Communications, Vol 11, Iss 1, Pp 1-12 (2020) Nature Communications |
| ISSN: | 2041-1723 |
| Popis: | 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. Chronic stress is a risk factor for mood disorders, yet the molecular and circuit mechanisms of stress-induced changes are not well understood. Here, the authors report the role of the transcription factor ΔFosB in driving activity changes in response to stress in glutamatergic neurons in the ventral hippocampus that project to nucleus accumben. |
| Databáze: | OpenAIRE |
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