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Cited by 87Treatment of Major DepressionStress Responses and CortisolNeurotransmitter Receptor Influence on Behavior

Functional Contribution of the Medial Prefrontal Circuitry in Major Depressive Disorder and Stress-Induced Depressive-Like Behaviors

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Bittar, Thibault P., Labonté, Benoit·2021·Frontiers in Behavioral Neuroscience
DOI 10.3389/fnbeh.2021.699592PMC PMC8257081
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Abstract

Despite decades of research on the neurobiology of major depressive disorder (MDD), the mechanisms underlying its expression remain unknown. The medial prefrontal cortex (mPFC), a hub region involved in emotional processing and stress response elaboration, is highly impacted in MDD patients and animal models of chronic stress. Recent advances showed alterations in the morphology and activity of mPFC neurons along with profound changes in their transcriptional programs. Studies at the circuitry level highlighted the relevance of deciphering the contributions of the distinct prefrontal circuits in the elaboration of adapted and maladapted behavioral responses in the context of chronic stress. Interestingly, MDD presents a sexual dimorphism, a feature recognized in the molecular field but understudied on the circuit level. This review examines the recent literature and summarizes the contribution of the mPFC circuitry in the expression of MDD in males and females along with the morphological and functional alterations that change the activity of these neuronal circuits in human MDD and animal models of depressive-like behaviors.

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  • Dysregulation of mPFC activity, particularly within L5 projection neurons, is implicated in the pathophysiology of depression through clinical imaging and preclinical models.

    “Dysregulation of mPFC activity—particularly within layer 5 (L5) projection neurons—has been implicated in the pathophysiology of depression through both clinical imaging studies and preclinical models [12–14].”

    From A nucleus accumbens-projecting prefrontal cortex circuit underlies chronic social stress-induced depression-like behaviors (2026) · cites this paper as [12]

    The Introduction reports altered mPFC activity in patients with major depressive disorder, and the E/I Balance Integrity section links mPFC pyramidal-neuron activity to depressive-like behaviors in animal models. The Laminar Organization section places some projection neurons in layer V, but the paper does not establish that layer V projection neurons in particular are implicated by both the clinical imaging and preclinical evidence. Page numbers are unavailable in our copy. (LLM, conf=0.85)

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Cited by

Sorted by citations

Authors
Bittar, T. P., & Labonté, B.
Affiliations
Université Laval (CA)
ORCID
Bittar, Thibault P.
Venue
Frontiers in Behavioral Neuroscience
Publisher
Frontiers Media SA
Published
2021-06-21
Volume
15
Pages
699592-699592
ISSN
1662-5153 (ISSN-L)
DOI
10.3389/fnbeh.2021.699592
PMC
PMC8257081
OpenAlex
W3175615431
Cited by
87
References
34
Citations by year
2026: 8 · 2025: 21 · 2024: 27 · 2023: 19 · 2022: 8 · 2021: 4
FWCI
1.84
Type
journal article
Language
en
Open access
Licence
Locations
  • Frontiers in Behavioral Neuroscience (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • National Alliance for Research on Schizophrenia and Depression
  • Canadian Institutes of Health Research (SVB397205)
  • Fonds de Recherche du Québec - Santé (RGPIN-2019-06496)
Topics
  • Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
  • Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
Keywords
major depressive disorder, medial prefrontal cortex, chronic stress, sexual dimorphism, neuronal morphology, transcriptional programs, animal models of depression

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