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Anterior cingulate cortex parvalbumin and somatostatin interneurons shape social behavior in male mice

Author

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  • Chuchu Qi

    (Fourth Military Medical University)

  • Wenqi Sima

    (Fourth Military Medical University)

  • Honghui Mao

    (Fourth Military Medical University)

  • Erling Hu

    (Fourth Military Medical University)

  • Junye Ge

    (Fourth Military Medical University)

  • Mao Deng

    (Chinese Academy of Sciences)

  • Andi Chen

    (Fourth Military Medical University)

  • Weiyi Ye

    (Chinese Academy of Sciences)

  • Qian Xue

    (Fourth Military Medical University)

  • Wenting Wang

    (Fourth Military Medical University
    Fourth Military Medical University)

  • Qian Chen

    (Chinese Academy of Sciences)

  • Shengxi Wu

    (Fourth Military Medical University)

Abstract

The anterior cingulate cortex (ACC) is essential for social behavior, and its dysfunction is implicated in social interaction deficits in autism. Pyramidal neuron activity in the ACC is modulated by parvalbumin (PV) and somatostatin (SST) interneurons, though their specific roles in social interactions remain unclear. Here, we demonstrate that PV and SST interneurons differentially contribute to the regulation of social interactions. In a Shank3-deficient autistic model, the expression of Kcnh7, a risk gene for autism, is reduced in both PV and SST interneurons. Knocking out Kcnh7 in either interneuron subtype leads to social interaction deficits. Furthermore, projections from the lateral posterior thalamic nucleus (mediorostral part, LPMR) to PV interneurons and from the ventral hippocampus (vHPC) to SST interneurons differentially modulate social interactions. These findings provide new insights into the distinct roles of PV and SST interneurons in social processes and their contributions to autism-related pathophysiology.

Suggested Citation

  • Chuchu Qi & Wenqi Sima & Honghui Mao & Erling Hu & Junye Ge & Mao Deng & Andi Chen & Weiyi Ye & Qian Xue & Wenting Wang & Qian Chen & Shengxi Wu, 2025. "Anterior cingulate cortex parvalbumin and somatostatin interneurons shape social behavior in male mice," Nature Communications, Nature, vol. 16(1), pages 1-18, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-59473-z
    DOI: 10.1038/s41467-025-59473-z
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    as
    1. Xiaoming Wang & Alexandra L. Bey & Brittany M. Katz & Alexandra Badea & Namsoo Kim & Lisa K. David & Lara J. Duffney & Sunil Kumar & Stephen D. Mague & Samuel W. Hulbert & Nisha Dutta & Volodya Hayrap, 2016. "Altered mGluR5-Homer scaffolds and corticostriatal connectivity in a Shank3 complete knockout model of autism," Nature Communications, Nature, vol. 7(1), pages 1-18, September.
    2. Yuan Mei & Patricia Monteiro & Yang Zhou & Jin-Ah Kim & Xian Gao & Zhanyan Fu & Guoping Feng, 2016. "Adult restoration of Shank3 expression rescues selective autistic-like phenotypes," Nature, Nature, vol. 530(7591), pages 481-484, February.
    3. Adam Kepecs & Gordon Fishell, 2014. "Interneuron cell types are fit to function," Nature, Nature, vol. 505(7483), pages 318-326, January.
    4. Vijendra Sharma & Rapita Sood & Abdessattar Khlaifia & Mohammad Javad Eslamizade & Tzu-Yu Hung & Danning Lou & Azam Asgarihafshejani & Maya Lalzar & Stephen J. Kiniry & Matthew P. Stokes & Noah Cohen , 2020. "eIF2α controls memory consolidation via excitatory and somatostatin neurons," Nature, Nature, vol. 586(7829), pages 412-416, October.
    5. J. Gray Camp & Keisuke Sekine & Tobias Gerber & Henry Loeffler-Wirth & Hans Binder & Malgorzata Gac & Sabina Kanton & Jorge Kageyama & Georg Damm & Daniel Seehofer & Lenka Belicova & Marc Bickle & Ric, 2017. "Multilineage communication regulates human liver bud development from pluripotency," Nature, Nature, vol. 546(7659), pages 533-538, June.
    6. Hunter F. Iaccarino & Annabelle C. Singer & Anthony J. Martorell & Andrii Rudenko & Fan Gao & Tyler Z. Gillingham & Hansruedi Mathys & Jinsoo Seo & Oleg Kritskiy & Fatema Abdurrob & Chinnakkaruppan Ad, 2016. "Gamma frequency entrainment attenuates amyloid load and modifies microglia," Nature, Nature, vol. 540(7632), pages 230-235, December.
    7. Matt Udakis & Victor Pedrosa & Sophie E. L. Chamberlain & Claudia Clopath & Jack R. Mellor, 2020. "Interneuron-specific plasticity at parvalbumin and somatostatin inhibitory synapses onto CA1 pyramidal neurons shapes hippocampal output," Nature Communications, Nature, vol. 11(1), pages 1-17, December.
    8. Nao Utashiro & Duncan Archibald Allan MacLaren & Yu-Chao Liu & Kaneschka Yaqubi & Birgit Wojak & Hannah Monyer, 2024. "Long-range inhibition from prelimbic to cingulate areas of the medial prefrontal cortex enhances network activity and response execution," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
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