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Peer-reviewedCC BY-NC-ND 4.0Nature Communications

Entrainment of prefrontal theta synchrony increases interbrain coupling and enhances social interaction in mouse models of autism

  • Eunkyu Hwang1
  • Soogeun Shin1
  • Anjin Lee2
  • Woohyun Kim1,3
  • Hyung-Geun Yoon1
  • Younghoon Kwon1
  • Dongseok Seo1
  • Dohoung Kim4
  • Eunjoon Kim3,5
  • Eunee Lee1
5 affiliations
  1. 1Department of Anatomy, Graduate School of Medical Science, Brain Korea 21 Project, Yonsei University College of Medicine, Seoul, Republic of Korea
  2. 2Yonsei University College of Medicine, Seoul, Republic of Korea
  3. 3Center for Synaptic Brain Dysfunctions, Institute for Basic Science (IBS), Daejeon, Republic of Korea
  4. 4Department of Convergence IT Engineering, Pohang University of Science and Technology, Pohang, Republic of Korea
  5. 5Department of Biological Sciences, Korea Advanced Institute for Science and Technology (KAIST), Daejeon, Republic of Korea
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Abstract

Social interaction requires the integration of information about self, other, and shared context. One of the proposed mechanisms supporting this coordination is interbrain synchrony – correlated neural activity between interacting individuals – yet its role in shaping social behavior remains unresolved. Here, we show that theta band synchrony in the medial prefrontal cortex (mPFC) is closely linked to social interaction in mice and often precedes its onset. In male Shank2 mutant mice, a genetic model of social dysfunction, mPFC interbrain synchrony was diminished, along with a reduced population of mPFC neurons encoding multiple dimensions of social information. Optogenetic entrainment of theta synchrony was accompanied by increased interbrain coupling and social interaction in male Shank2-/- and Tbr1+/K228E mutant mice, two well-established genetic models of autism spectrum disorder (ASD). These findings identify prefrontal theta synchrony as a neural substrate that supports social behavior and provide a framework for understanding how coordinated neural activity across brains contributes to social interaction.

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Cite

BibTeXRIS
BibTeX
@article{hwang2026entrainment,
  title = {{Entrainment of prefrontal theta synchrony increases interbrain coupling and enhances social interaction in mouse models of autism}},
  author = {Eunkyu Hwang and Soogeun Shin and Anjin Lee and Woohyun Kim and Hyung-Geun Yoon and Younghoon Kwon and Dongseok Seo and Dohoung Kim and Eunjoon Kim and Eunee Lee},
  journal = {Nature Communications},
  year = {2026},
  month = sep,
  doi = {10.1038/s41467-026-77939-6},
  url = {https://doi.org/10.1038/s41467-026-77939-6},
  note = {CC BY-NC-ND 4.0},
}
RIS
TY  - JOUR
TI  - Entrainment of prefrontal theta synchrony increases interbrain coupling and enhances social interaction in mouse models of autism
AU  - Eunkyu Hwang
AU  - Soogeun Shin
AU  - Anjin Lee
AU  - Woohyun Kim
AU  - Hyung-Geun Yoon
AU  - Younghoon Kwon
AU  - Dongseok Seo
AU  - Dohoung Kim
AU  - Eunjoon Kim
AU  - Eunee Lee
PY  - 2026
DA  - 2026/09/24
JO  - Nature Communications
DO  - 10.1038/s41467-026-77939-6
UR  - https://doi.org/10.1038/s41467-026-77939-6
AB  - Social interaction requires the integration of information about self, other, and shared context. One of the proposed mechanisms supporting this coordination is interbrain synchrony – correlated neural activity between interacting individuals – yet its role in shaping social behavior remains unresolved. Here, we show that theta band synchrony in the medial prefrontal cortex (mPFC) is closely linked to social interaction in mice and often precedes its onset. In male Shank2 mutant mice, a genetic model of social dysfunction, mPFC interbrain synchrony was diminished, along with a reduced population of mPFC neurons encoding multiple dimensions of social information. Optogenetic entrainment of theta synchrony was accompanied by increased interbrain coupling and social interaction in male Shank2-/- and Tbr1+/K228E mutant mice, two well-established genetic models of autism spectrum disorder (ASD). These findings identify prefrontal theta synchrony as a neural substrate that supports social behavior and provide a framework for understanding how coordinated neural activity across brains contributes to social interaction.
SN  - 2041-1723
ER  -