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Cortical representations of affective pain shape empathic fear in male mice

Author

Listed:
  • Jiye Choi

    (Institute for Basic Science (IBS))

  • Young-Beom Lee

    (Institute for Basic Science (IBS))

  • Dahm So

    (Institute for Basic Science (IBS)
    Korea Advanced Institute of Science and Technology (KAIST))

  • Jee Yeon Kim

    (Institute for Basic Science (IBS))

  • Sungjoon Choi

    (Institute for Basic Science (IBS))

  • Sowon Kim

    (Institute for Basic Science (IBS))

  • Sehoon Keum

    (Institute for Basic Science (IBS))

Abstract

Affect sharing, the ability to vicariously feel others’ emotions, constitutes the primary component of empathy. However, the neural basis for encoding others’ distress and representing shared affective experiences remains poorly understood. Here, using miniature endoscopic calcium imaging, we identify distinct and dynamic neural ensembles in the anterior cingulate cortex (ACC) that encode observational fear across both excitatory and inhibitory neurons in male mice. Notably, we discover that the population dynamics encoding vicarious freezing information are conserved in ACC pyramidal neurons and are specifically represented by affective, rather than sensory, responses to direct pain experience. Furthermore, using circuit-specific imaging and optogenetic manipulations, we demonstrate that distinct populations of ACC neurons projecting to the periaqueductal gray (PAG), but not to the basolateral amygdala (BLA), selectively convey affective pain information and regulate observational fear. Taken together, our findings highlight the critical role of ACC neural representations in shaping empathic freezing through the encoding of affective pain.

Suggested Citation

  • Jiye Choi & Young-Beom Lee & Dahm So & Jee Yeon Kim & Sungjoon Choi & Sowon Kim & Sehoon Keum, 2025. "Cortical representations of affective pain shape empathic fear in male mice," Nature Communications, Nature, vol. 16(1), pages 1-15, December.
  • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-57230-w
    DOI: 10.1038/s41467-025-57230-w
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    References listed on IDEAS

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    1. Ziyan Huang & Myung Chung & Kentaro Tao & Akiyuki Watarai & Mu-Yun Wang & Hiroh Ito & Teruhiro Okuyama, 2023. "Ventromedial prefrontal neurons represent self-states shaped by vicarious fear in male mice," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    2. Tetsuya Sakaguchi & Satoshi Iwasaki & Mami Okada & Kazuki Okamoto & Yuji Ikegaya, 2018. "Ethanol facilitates socially evoked memory recall in mice by recruiting pain-sensitive anterior cingulate cortical neurons," Nature Communications, Nature, vol. 9(1), pages 1-10, December.
    3. Chong Chen & Jesse K. Niehaus & Fatih Dinc & Karen L. Huang & Alexander L. Barnette & Adrien Tassou & S. Andrew Shuster & Lihua Wang & Andrew Lemire & Vilas Menon & Kimberly Ritola & Adam W. Hantman &, 2024. "Neural circuit basis of placebo pain relief," Nature, Nature, vol. 632(8027), pages 1092-1100, August.
    4. Marc T. Pisansky & Leah R. Hanson & Irving I. Gottesman & Jonathan C. Gewirtz, 2017. "Oxytocin enhances observational fear in mice," Nature Communications, Nature, vol. 8(1), pages 1-11, December.
    5. Patricia H. Janak & Kay M. Tye, 2015. "From circuits to behaviour in the amygdala," Nature, Nature, vol. 517(7534), pages 284-292, January.
    6. Jan Haaker & Jonathan Yi & Predrag Petrovic & Andreas Olsson, 2017. "Endogenous opioids regulate social threat learning in humans," Nature Communications, Nature, vol. 8(1), pages 1-9, August.
    7. Shana E. Silverstein & Ruairi O’Sullivan & Olena Bukalo & Dipanwita Pati & Julia A. Schaffer & Aaron Limoges & Leo Zsembik & Takayuki Yoshida & John J. O’Malley & Ronald F. Paletzki & Abby G. Lieberma, 2024. "A distinct cortical code for socially learned threat," Nature, Nature, vol. 626(8001), pages 1066-1072, February.
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