Neural networks of the mouse visceromotor cortex

Houri Hintiryan^#¹, Muye Zhu^#^{1

2}, Pingping Zhao³, Mingmin Zhang^{4

5}, Joshua Barry⁶, Sumit Nanda¹, Mitchell Rudd¹, Angela Wong⁴, Samara Miller³, Lin Gou¹, Jinxing Wei⁷, Brian Zingg¹, Jiandong Sun¹, Adriana Gutierrez¹, Hyun-Seung Mun¹, Yeji E Han¹, Ian Bowman¹, Luis Garcia¹, Darrick Lo¹, Tyler Boesen¹, Chunru Cao¹, Qiuying Zhao¹, Nicholas N Foster¹, Keivan Moradi¹, Seita Yamashita¹, Christian Estrada¹, Aishwarya Dev¹, Jennifer Gonzalez¹, Hanpeng Xu¹, Gavin Yang¹, Chang Sin Park^{8

9}, X William Yang^{8

9}, Michael S Levine⁶, Li I Zhang⁷, Paul Micevych⁴, Carlos Cepeda⁶, Peyman Golshani^{3

10}, Weizhe Hong^{4

5}, Hong-Wei Dong¹¹

Affiliations

¹ UCLA Brain Research & Artificial Intelligence Nexus, Department of Neurobiology, David Geffen School of Medicine at UCLA, University of California Los Angeles, Los Angeles, CA, USA.
² Google, Boulder, CO, USA.
³ Department of Neurology, David Geffen School of Medicine at UCLA, University of California Los Angeles, Los Angeles, CA, USA.
⁴ Department of Neurobiology, David Geffen School of Medicine at UCLA, University of California Los Angeles, Los Angeles, CA, USA.
⁵ Department of Biological Chemistry, David Geffen School of Medicine at UCLA, University of California Los Angeles, Los Angeles, CA, USA.
⁶ IDDRC, Jane and Terry Semel Institute for Neuroscience and Human Behavior, Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine at UCLA, University of California Los Angeles, Los Angeles, CA, USA.
⁷ Center for Neural Circuits and Sensory Processing Disorders, Zilkha Neurogenetic Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
⁸ Center for Neurobehavioral Genetics, Semel Institute for Neuroscience & Human Behavior, University of California Los Angeles, Los Angeles, CA, USA.
⁹ Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine at UCLA, University of California Los Angeles, Los Angeles, CA, USA.
¹⁰ Greater Los Angeles VA Medical Center, Los Angeles, CA, USA.
¹¹ UCLA Brain Research & Artificial Intelligence Nexus, Department of Neurobiology, David Geffen School of Medicine at UCLA, University of California Los Angeles, Los Angeles, CA, USA. HongWeiD@mednet.ucla.edu.

^# Contributed equally.

PMID: 40866707
DOI: 10.1038/s41586-025-09360-w

Neural networks of the mouse visceromotor cortex

Houri Hintiryan et al. Nature. 2025.

. 2025 Aug 27.

doi: 10.1038/s41586-025-09360-w. Online ahead of print.

Authors

Affiliations

¹ UCLA Brain Research & Artificial Intelligence Nexus, Department of Neurobiology, David Geffen School of Medicine at UCLA, University of California Los Angeles, Los Angeles, CA, USA.
² Google, Boulder, CO, USA.
³ Department of Neurology, David Geffen School of Medicine at UCLA, University of California Los Angeles, Los Angeles, CA, USA.
⁴ Department of Neurobiology, David Geffen School of Medicine at UCLA, University of California Los Angeles, Los Angeles, CA, USA.
⁵ Department of Biological Chemistry, David Geffen School of Medicine at UCLA, University of California Los Angeles, Los Angeles, CA, USA.
⁶ IDDRC, Jane and Terry Semel Institute for Neuroscience and Human Behavior, Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine at UCLA, University of California Los Angeles, Los Angeles, CA, USA.
⁷ Center for Neural Circuits and Sensory Processing Disorders, Zilkha Neurogenetic Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
⁸ Center for Neurobehavioral Genetics, Semel Institute for Neuroscience & Human Behavior, University of California Los Angeles, Los Angeles, CA, USA.
⁹ Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine at UCLA, University of California Los Angeles, Los Angeles, CA, USA.
¹⁰ Greater Los Angeles VA Medical Center, Los Angeles, CA, USA.
¹¹ UCLA Brain Research & Artificial Intelligence Nexus, Department of Neurobiology, David Geffen School of Medicine at UCLA, University of California Los Angeles, Los Angeles, CA, USA. HongWeiD@mednet.ucla.edu.

^# Contributed equally.

PMID: 40866707
DOI: 10.1038/s41586-025-09360-w

Abstract

The medial prefrontal cortex (MPF) regulates autonomic and neuroendocrine responses to stress^1,2 and coordinates goal-directed behaviours such as attention, decision-making and social interactions^3-8. However, the underlying mechanisms remain unclear due to incomplete circuit-level MPF characterization⁷. Here, using integrated neuroanatomical, physiological and behavioural approaches, we construct a comprehensive wiring diagram of the MPF, focused on the dorsal peduncular area (DP)-a poorly understood prefrontal area. We identify its deep (DPd) and superficial (DPs) layers, along with the infralimbic area, as major components of the visceromotor cortex that directly project to hypothalamic and brainstem structures to govern neuroendocrine, sympathetic and parasympathetic output. Notably, the DP functions as a network hub integrating diverse cortical inputs and modulating goal-directed behaviour through a largely unidirectional cortical information flow. On the basis of the mesoscale MPF connectome, we propose a unified network model in which distinct MPF areas orchestrate physiological and behavioural responses to internal and external stimuli.

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Conflict of interest statement

Competing interests: The authors declare no competing interests.

Update of

Neural Networks of the Mouse Primary Visceromotor Cortex.
Dong HW, Hintiryan H, Zhu M, Zhao P, Zhang M, Barry J, Nanda S, Rudd M, Wong A, Miller S, Gou L, Wei J, Zingg B, Sun J, Gutierrez A, Mun HS, Bowman I, Garcia L, Lo D, Boesen T, Cao C, Zhao Q, Foster N, Moradi K, Yamashita S, Estrada C, Dev A, Gonzalez J, Xu H, Yang G, Park C, Yang X, Levine M, Zhang L, Micevych P, Cepeda C, Golshani P, Hong W, Yang Y. Dong HW, et al. Res Sq [Preprint]. 2025 Apr 28:rs.3.rs-4125909. doi: 10.21203/rs.3.rs-4125909/v1. Res Sq. 2025. Update in: Nature. 2025 Aug 27. doi: 10.1038/s41586-025-09360-w. PMID: 40343331 Free PMC article. Updated. Preprint.

References

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Neural networks of the mouse visceromotor cortex

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Neural networks of the mouse visceromotor cortex

Authors

Affiliations

Abstract

Conflict of interest statement

Update of

References

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