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Prefrontal cortex circuits in depression and anxiety: contribution of discrete neuronal populations and target regions
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Our understanding of depression and its treatment has advanced with the advent of ketamine as a rapid-acting antidepressant and the development and refinement of tools capable of selectively altering the activity of populations of neuronal subtypes. This work has resulted in a paradigm shift away from dysregulation of single neurotransmitter systems in depression towards circuit level abnormalities impacting function across multiple brain regions and neurotransmitter systems. Studies on the features of circuit level abnormalities demonstrate structural changes within the prefrontal cortex (PFC) and functional changes in its communication with distal brain structures. Treatments that impact the activity of brain regions, such as transcranial magnetic stimulation or rapid-acting antidepressants like ketamine, appear to reverse depression associated circuit abnormalities though the mechanisms underlying the reversal, as well as development of these abnormalities remains unclear. Recently developed optogenetic and chemogenetic tools that allow high-fidelity control of neuronal activity in preclinical models have begun to elucidate the contributions of the PFC and its circuitry to depression- and anxiety-like behavior. These tools offer unprecedented access to specific circuits and neuronal subpopulations that promise to offer a refined view of the circuit mechanisms surrounding depression and potential mechanistic targets for development and reversal of depression associated circuit abnormalities.
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“these changes in neural circuitry are believed to underlie the deficits in learning/memory, mood, motivation, and reward seeking that are characteristic of depression and related disorders (10, 67–74)”
From Psychedelics and Other Psychoplastogens for Treating Mental Illness. (2021) · cites this paper as [74]
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Metadata
- Authors
- Hare, B. D., & Duman, R. S.
- Affiliations
- Yale University (US)
- Corresponding author
- Hare, Brendan D.
- Venue
- Molecular Psychiatry
- Published
- 2020-02-21
- Volume
- 25
- Issue
- 11
- Pages
- 2742-2758
- ISSN
- 1359-4184 (ISSN-L)
- 1476-5578
- PMC
- PMC7442605
- OpenAlex
- W3007694136
- Cited by
- 366
- References
- 128
- Citations by year
- 2026: 33 · 2025: 69 · 2024: 67 · 2023: 65 · 2022: 66 · 2021: 55 · 2020: 11
- FWCI
- 6.49
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Molecular Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (R01 MH105910-04, RO1 MH093897-06A1)
- Brain and Behavior Research Foundation (NARSAD to BH)
- Topics
- Health Sciences › Medicine › Pharmacology (medical) › 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
- prefrontal cortex, depression, anxiety, neural circuits, neuronal subpopulations, ketamine, rapid-acting antidepressants, transcranial magnetic stimulation, optogenetics, chemogenetics, depression-like behavior, anxiety-like behavior, neurotransmitter systems
- MeSH terms
- Antidepressive Agents, Anxiety, Depression, Ketamine, Neural Pathways, Prefrontal Cortex
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