Cell
Volume 170, Issue 2, 13 July 2017, Pages 284-297.e18
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Article
Distinct Ventral Pallidal Neural Populations Mediate Separate Symptoms of Depression

https://doi.org/10.1016/j.cell.2017.06.015Get rights and content
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Highlights

  • VP PV neurons project to the LHb and VTA and release different transmitters

  • Elevated VP PV neuronal activity is a hallmark of depressed animals

  • VP PV neurons mediate distinct depressive-like symptoms based on projection target

Summary

Major depressive disorder (MDD) patients display a common but often variable set of symptoms making successful, sustained treatment difficult to achieve. Separate depressive symptoms may be encoded by differential changes in distinct circuits in the brain, yet how discrete circuits underlie behavioral subsets of depression and how they adapt in response to stress has not been addressed. We identify two discrete circuits of parvalbumin-positive (PV) neurons in the ventral pallidum (VP) projecting to either the lateral habenula or ventral tegmental area contributing to depression. We find that these populations undergo different electrophysiological adaptations in response to social defeat stress, which are normalized by antidepressant treatment. Furthermore, manipulation of each population mediates either social withdrawal or behavioral despair, but not both. We propose that distinct components of the VP PV circuit can subserve related, yet separate depressive-like phenotypes in mice, which could ultimately provide a platform for symptom-specific treatments of depression.

Keywords

ventral pallidum
social defeat stress
parvalbumin
neural circuits
equine infectious anemia virus
depression
susceptibility

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