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Distinct subpopulations of parvalbumin neurons participating in divergent prefrontal functions

Neuropsychopharmacology volume 50, pages 1502–1514 (2025)Cite this article

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Abstract

Prefrontal parvalbumin (PV) neurons play crucial roles in various distinct functions, while malfunction of PV-neurons also has critical contributions to various brain diseases, including both psychiatric and neurodegenerative disorders. However, whether the prefrontal cortex (PFC) PV-neurons participating in these functions and malfunctions are distinct subpopulations is not well understood. This question is important for a better understanding of both the basic properties/function of PV-neurons and inhibitory neurons in general, and for potential comorbid occurrence of dysfunctions in disease settings. Here, we analyzed dorsomedial prefrontal cortex (dmPFC) PV-neurons participating in working memory, modulation of conditioned fear memory, and anxiety, regarding their relative localization, electrophysiological properties, and synaptic inputs. In addition, by using activity-dependent tagging method, we examined whether manipulating the dmPFC PV-neurons participating in one function may affect another function as a way to test for potential functional interactions between them. We found that: (1) one single group of dmPFC PV-neurons participating in the two forms of modulation of conditioned fear memory, based on their high overlap in localization and mutual functional interactions with each other. (2) dmPFC PV-neurons participating in fear memory modulation and anxiety are two different subpopulations, with unique electrophysiological properties. (3) dmPFC PV-neurons participating in working memory and fear memory modulation are two different subpopulations, with different synaptic and neuronal properties. These findings provide important insights into the organization of PV-neurons in the PFC and highlight the distinct and non-interacting nature of different PV-subpopulations in the PFC functional diversity.

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Fig. 1: The same dmPFC PV-neuron population participate in both SL and 50 P.
Fig. 2: Two distinct dmPFC PV-neuron subpopulations participate in EPM behavior or modulation of fear memory, with distinct synaptic inputs.
Fig. 3: Comparison between neuronal properties of PV-neurons participating in 50 P and EPM.
Fig. 4: Localization of dmPFC PV-neurons activated by WM and SL.
Fig. 5: Different contributions to behavioral tasks and neuronal properties of dmPFC PV-neurons participating in SL and WM.

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Data availability

The data supporting the findings of this study are available within the paper and its Supplementary Materials.

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Funding

This work is supported by grant from Shenzhen-Hong Kong Institute of Brain Science-Shenzhen Fundamental Research Institutions (2024SHIBS0004), National Natural Science Foundation of China (82204356), Shenzhen Government Basic Research Grant (JCYJ20220530160001002) and Shenzhen Children’s Hospital Fund (ynkt2021-zz24).

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Authors and Affiliations

  1. School of Chemical Biology and Biotechnology, Peking University Shenzhen Graduate School, Shenzhen, China

    Yehong Hu, Xinyang Zhang, Tsz Hei Fong, Tianyu Wang, Jin Zhang & Qiang Zhou

  2. School of Basic Medical Sciences, Xi’an Medical University, Xi’an, China

    Jin Zhang

  3. Pediatric Neurology, Shenzhen Children’s Hospital, Shenzhen, China

    Yujie Zhang

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  1. Yehong Hu
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Contributions

Conceptualization: QZ, YH, JZ and XZ. Methodology: QZ, YH, JZ and XZ. Experiment and data analysis: YH, XZ, THF, TW, JZ and QZ. Writing: QZ, YH, YZ and XZ. Review and editing: QZ, YH, YZ and THF. Funding acquisition: QZ, JZ and YZ. Project administration: QZ. Supervision, QZ.

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Correspondence to Qiang Zhou.

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Hu, Y., Zhang, X., Fong, T.H. et al. Distinct subpopulations of parvalbumin neurons participating in divergent prefrontal functions. Neuropsychopharmacol. 50, 1502–1514 (2025). https://doi.org/10.1038/s41386-025-02159-3

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