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journal article·2026-06-04Open access

A Brain‐Wide Atlas of Astrocytic Oxytocin Receptors Reveals a Glial Basis for Nucleus Accumbens Modulation of Affiliative Behavior

Clémence Denis, Stefan Stojilkovic, Kai‐Yi Wang, Cristina Márquez, Annabel C. Kleinwächter, Angel Baudon, Yuval Podpecan, Aurélia Ces, Mélanie Kremer, Isabelle Arnoux, Nathalie Rouach, Jemima Helen, Sophie Trender, Andreas Wallkum, Selina Wunsch, Franziska Schommer, Moritz C. Wimmer, Tim Schubert, Felix Franke, Jabir Aliyu Muhammad, Eva M. Eisemann, Ingrid Camila Possa‐Paranhos, Cassandra Baumann, Pierre‐Alexis Derrien, Quirin Krabichler, Cosmo Garcia, Henning Fröhlich, Matthew K. Kirchner, Valery Grinevich, Pascal Darbon, Javier E. Stern, Ferdinand Althammer, Alexandre Charlet

Advanced Science
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Abstract

ABSTRACT Until recently, it was widely assumed that oxytocin signaling occurred exclusively through the activation of neuronal oxytocin receptors, with neurons being the primary targets of released oxytocin. However, this view was challenged by the discovery of functional oxytocin receptors in central amygdala astrocytes, which are essential for the proper function of local neuronal microcircuits. Since then, astrocytic oxytocin receptors have been implicated in various aspects of rodent physiology and behavior, yet it remains unclear whether this mechanism is region‐specific or widespread across the brain. Here, we provide extensive anatomical data on oxytocin receptor expression in mice and rats, functionally validated through calcium imaging. Based on this mapping and using genetic, calcium imaging and behavioral approaches, we further demonstrate a critical role for oxytocin receptor‐expressing astrocytes in the nucleus accumbens in social behavior. In summary, our findings demonstrate that oxytocin receptors are widely expressed in astrocytes across different brain regions. In the nucleus accumbens, these receptors modulate social behavior—an observation with significant implications for the current model of oxytocinergic modulation in the brain.
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Research context

OpenAlex topics: Neuroendocrine regulation and behavior · Neuroscience of respiration and sleep · Neurogenesis and neuroplasticity mechanisms

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Affiliations

Centre National de La Recherche Scientifique and University of Strasbourg Institute of Cellular and Integrative Neuroscience Strasbourg France

Institute of Human Genetics Heidelberg University Heidelberg Germany

Center For Neuroscience and Cell Biology CNC‐UC University of Coimbra Coimbra Portugal

Centre For Innovative Biomedicine and Biotechnology University of Coimbra Coimbra Portugal

Center for Interdisciplinary Research in Biology Collège de France, CNRS, INSERM, PSL‐Neuro, Université PSL Paris France

Department of Neuropeptide Research in Psychiatry Central Institute of Mental Health German Center for Psychiatry Medical Faculty Mannheim University of Heidelberg Mannheim Germany

Center For Neuroinflammation and Cardiometabolic Diseases, and Neuroscience Institute Georgia State University Atlanta Georgia USA

International Joint Laboratory for Translational Research on Neuromodulation, Shenzhen Institutes of Advanced Technology Chinese Academy of Sciences Shenzhen China

Funding

Centre National de la Recherche Scientifique · Université de Strasbourg

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