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Cited by 21Stress Responses and CortisolNeuroscience and Neuropharmacology ResearchMemory and Neural Mechanisms

Circuit- and laminar-specific regulation of medial prefrontal neurons by chronic stress

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Liu, Wei-Zhu, Wang, Chun-Yan, Wang, Yu, Cai, Mei-Ting, Zhong, Wei-Xiang, Liu, Tian, Wang, Zhi-Hao, Pan, Han-Qing +2 more·2023·Cell & Bioscience
DOI 10.1186/s13578-023-01050-2PMC PMC10197342
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Abstract

Background: Chronic stress exposure increases the risk of mental health problems such as anxiety and depression. The medial prefrontal cortex (mPFC) is a hub for controlling stress responses through communicating with multiple limbic structures, including the basolateral amygdala (BLA) and nucleus accumbens (NAc). However, considering the complex topographical organization of the mPFC neurons in different subregions (dmPFC vs. vmPFC) and across multiple layers (Layer II/III vs. Layer V), the exact effects of chronic stress on these distinct mPFC output neurons remain largely unknown. Results: We first characterized the topographical organization of mPFC neurons projecting to BLA and NAc. Then, by using a typical mouse model of chronic restraint stress (CRS), we investigated the effects of chronic stress on the synaptic activity and intrinsic properties of the two mPFC neuronal populations. Our results showed that there was limited collateralization of the BLA- and NAc-projecting pyramidal neurons, regardless of the subregion or layer they were situated in. CRS significantly reduced the inhibitory synaptic transmission onto the BLA-projecting neurons in dmPFC layer V without any effect on the excitatory synaptic transmission, thus leading to a shift of the excitation-inhibition (E-I) balance toward excitation. However, CRS did not affect the E-I balance in NAc-projecting neurons in any subregions or layers of mPFC. Moreover, CRS also preferentially increased the intrinsic excitability of the BLA-projecting neurons in dmPFC layer V. By contrast, it even caused a decreasing tendency in the excitability of NAc-projecting neurons in vmPFC layer II/III. Conclusion: Our findings indicate that chronic stress exposure preferentially modulates the activity of the mPFC-BLA circuit in a subregion (dmPFC) and laminar (layer V) -dependent manner.

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  • mPFC L5 neurons are heterogeneous in molecular marker, synaptic properties, projection targets, local circuit integration, and functional specialization.

    “mPFC L5 neurons are heterogenous populations, in terms of their molecular marker, synaptic properties, projection targets, local circuit integration, and functional specialization [15–18].”

    From A nucleus accumbens-projecting prefrontal cortex circuit underlies chronic social stress-induced depression-like behaviors (2026) · cites this paper as [17]

    The Results (Anatomical characterization; page unavailable) identify distinct BLA- and NAc-projecting populations in mPFC layer V. The Discussion (page unavailable) describes projection-dependent synaptic responses to stress and mentions molecular profiles and differing circuit functions. The paper does not establish heterogeneity in local circuit integration or specifically demonstrate molecular-marker differences among layer V neurons. (LLM, conf=0.84)

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Cited by

Sorted by citations

Authors
Liu, W.-Z., Wang, C.-Y., Wang, Y., Cai, M.-T., Zhong, W.-X., Liu, T., Wang, Z.-H., Pan, H.-Q., Zhang, W.-H., & Pan, B.-X.
Affiliations
Nanchang University (CN)
Corresponding author
Pan, Bing-Xing
ORCID
Venue
Cell & Bioscience
Publisher
Springer Science and Business Media LLC
Published
2023-05-18
Volume
13
Issue
1
Pages
90-90
ISSN
2045-3701 (ISSN-L)
DOI
10.1186/s13578-023-01050-2
PMC
PMC10197342
OpenAlex
W4377139855
Cited by
21
References
9
Citations by year
2026: 10 · 2025: 7 · 2024: 4
FWCI
3.91
Type
journal article
Language
en
Open access
Licence
Locations
  • Cell & Bioscience (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • National Natural Science Foundation of China (82101589, 32160193, 31970953, 82125010, 81930032, 32222034)
  • China Postdoctoral Science Foundation (2021TQ0138, 2021M701545)
  • Natural Science Foundation of Jiangxi Province (20212ACB206038)
  • National Key R&D Program of China (2021ZD0202704)
Topics
  • Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
Keywords
chronic stress, medial prefrontal cortex, basolateral amygdala, nucleus accumbens, cortical layers, pyramidal neurons, synaptic inhibition, excitation-inhibition balance, intrinsic excitability, restraint stress, anxiety, depression

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