Endogenous oxytocin reconfigures brainwide network dynamics toward salience-related states

Abstract

Oxytocin (OXT) can exert diverse effects across social, affective and motivational domains, yet its impact on brain function at the systems level remains unclear. Here, we combine chemogenetics with fMRI and electrophysiology in mice to investigate how endogenous OXT reshapes intrinsic large-scale brain network dynamics. Using mice constitutively expressing hM3Dq DREADD receptors in OXT-releasing hypothalamic neurons, we show that chemogenetic stimulation of OXT neurons elicits widespread increases in cerebral blood volume, with prominent effects in fronto-striatal regions and dorsal hippocampal areas. This broad functional response is accompanied by a network-specific reconfiguration of brain-wide functional connectivity, characterized by increased coupling between key components of the rodent social brain, and negative functional coupling between hippocampal and fronto-cortical regions. In vivo electrophysiology under matched conditions shows concordant changes in slow (<1 Hz) and delta-band coherence across frontalthalamic and fronto-hippocampal circuits, revealing a plausible neural correlate of the observed connectivity effects. Notably, these changes are accompanied by a marked reconfiguration of the temporal architecture of fMRI network activity, with increased occupancy of co-activation states engaging saliencerelated regions and a concomitant suppression of sensory-dominated states. Together, these findings identify dynamic network-state reconfiguration as a systems-level mechanism through which endogenous OXT can tune functional communication across social-affective circuits.

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BibTeX RIS

BibTeX

@misc{guzman2026endogenous,
  title = {{Endogenous oxytocin reconfigures brainwide network dynamics toward salience-related states}},
  author = {E. A. de Guzman and C. Montani and A. Hayward and S. Migliarini and G. Morelli and D. Gutierrez-Barragan and A. Galbusera and F. Alvino and L. Coletta and Y. Kim and S. Panzeri and L. Cancedda and M. Pasqualetti and A. Gozzi},
  howpublished = {bioRxiv},
  year = {2026},
  month = sep,
  doi = {10.64898/2026.09.22.753403},
  url = {https://www.biorxiv.org/content/10.64898/2026.09.22.753403v1},
  note = {CC BY},
}

RIS

TY  - UNPB
TI  - Endogenous oxytocin reconfigures brainwide network dynamics toward salience-related states
AU  - E. A. de Guzman
AU  - C. Montani
AU  - A. Hayward
AU  - S. Migliarini
AU  - G. Morelli
AU  - D. Gutierrez-Barragan
AU  - A. Galbusera
AU  - F. Alvino
AU  - L. Coletta
AU  - Y. Kim
AU  - S. Panzeri
AU  - L. Cancedda
AU  - M. Pasqualetti
AU  - A. Gozzi
PY  - 2026
DA  - 2026/09/22
PB  - bioRxiv
DO  - 10.64898/2026.09.22.753403
UR  - https://www.biorxiv.org/content/10.64898/2026.09.22.753403v1
AB  - Oxytocin (OXT) can exert diverse effects across social, affective and motivational domains, yet its impact on brain function at the systems level remains unclear. Here, we combine chemogenetics with fMRI and electrophysiology in mice to investigate how endogenous OXT reshapes intrinsic large-scale brain network dynamics. Using mice constitutively expressing hM3Dq DREADD receptors in OXT-releasing hypothalamic neurons, we show that chemogenetic stimulation of OXT neurons elicits widespread increases in cerebral blood volume, with prominent effects in fronto-striatal regions and dorsal hippocampal areas. This broad functional response is accompanied by a network-specific reconfiguration of brain-wide functional connectivity, characterized by increased coupling between key components of the rodent social brain, and negative functional coupling between hippocampal and fronto-cortical regions. In vivo electrophysiology under matched conditions shows concordant changes in slow (<1 Hz) and delta-band coherence across frontalthalamic and fronto-hippocampal circuits, revealing a plausible neural correlate of the observed connectivity effects. Notably, these changes are accompanied by a marked reconfiguration of the temporal architecture of fMRI network activity, with increased occupancy of co-activation states engaging saliencerelated regions and a concomitant suppression of sensory-dominated states. Together, these findings identify dynamic network-state reconfiguration as a systems-level mechanism through which endogenous OXT can tune functional communication across social-affective circuits.
ER  -

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