Distinct Ventral Pallidal Neural Populations Mediate Separate Symptoms of Depression
Open accessAbstract
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.
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CSDS increases inhibitory transmission from the ventral pallidum-to-VTA, and inhibiting this circuit restored normal social interactions.
“CSDS also increases inhibitory transmission from the ventral pallidum-to-VTA, the importance of which was demonstrated by the finding that inhibiting this circuit restored normal social interactions [153].”
From Neural circuits regulating prosocial behaviors (2023) · cites this paper as [153]
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- Authors
- Knowland, D., Lilascharoen, V., Pacia, C. P., Shin, S., Wang, E. H.-J., & Lim, B. K.
- Affiliations
- University of California San Diego (US)
- Corresponding author
- Lim, Byung Kook
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2017-07
- Volume
- 170
- Issue
- 2
- Pages
- 284-297.e18
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC5621481
- OpenAlex
- W2724120353
- Cited by
- 273
- References
- 49
- Citations by year
- 2026: 21 · 2025: 27 · 2024: 32 · 2023: 34 · 2022: 32 · 2021: 33 · 2020: 37 · 2019: 27 · 2018: 22 · 2017: 7
- FWCI
- 17.76
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- Klingenstein foundation
- Searle scholar program
- Kinship foundation (15-SSP-229)
- Whitehall foundation (2014-08-63)
- NARSAD young investigator grant (24094)
- NIH (MH107742, MH108594)
- Anandamahidol Foundation Fellowship
- Topics
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- major depressive disorder, ventral pallidum, parvalbumin neurons, lateral habenula, ventral tegmental area, social defeat stress, social withdrawal, behavioral despair, antidepressant treatment, neural circuits
- MeSH terms
- Animals, Avoidance Learning, Depression, Major Depressive Disorder, Depressive Disorder, Major, Female, Male, Mesencephalon, Mice, Inbred C57BL, Neurons, Parvalbumins, Mice, Basal Forebrain, In Vitro Techniques
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