Acetylcholine drives astrocytic JAK2-STAT3 signaling to modulate male-to-female approach behavior
Year: 2026
Type: preprint
Abstract: Astrocytes are essential regulators of neural circuits and behavior, sensing synaptic activity and modulating plasticity through diverse intracellular mechanisms. However, the contribution of astrocyte transcription factor-based cascades, linking external stimuli to long-term transcriptional programs, is currently misunderstood. Here we show that the JAK2-STAT3 signaling plays a critical role in male-to-female social behavior. Hence, in male mice, exposure to estrus females rapidly and selectively induces STAT3 signaling in ventral hippocampal astrocytes. Surprisingly, this induction is not driven through canonical cytokine signaling but by septo-hippocampal cholinergic inputs acting through α7 nicotinic acetylcholine receptors (α7nAChR). Astrocytic α7nAChR-JAK2-STAT3 signaling in turn modulates vCA1 pyramidal neuron activity and is required for context-appropriate male approach behavior. These findings reveal a previously unsuspected cellular pathway integrating neuromodulatory inputs and transcription factor-based signaling to shape male behavioral response depending on female receptivity.
Institutions: Centre National de la Recherche Scientifique, Commissariat à l'Énergie Atomique et aux Énergies Alternatives, Université Paris-Saclay, Institut des Neurosciences Paris-Saclay, Laboratoire des Maladies Neurodégénératives, Molecular Imaging Research Center, Institut des Neurosciences Cellulaires et Intégratives, Université de Strasbourg, Aix-Marseille Université, Institut de Neurosciences de la Timone
Language: English
Subfield: Cellular and Molecular Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: green
Funders: Fondation Vaincre Alzheimer, Agence Nationale de la Recherche, Institut National de la Santé et de la Recherche Médicale, Université de Strasbourg, Centre National de la Recherche Scientifique, Université Paris-Saclay, National Institutes of Health, National Institute of Environmental Health Sciences
Awards: G1242383005, Unveiling the Impact of Ventral Hippocampal Astrocyte Signaling on Socio-Sexual Behavior in Mice, G325848743, G4016299606, G4728065207, Plasticity of fear conditioned analgesia, G4779185514, G6136357505, G6389594462, Multi-integrative role of oxytocin receptor signaling: effect on social behavior and social interaction disorders, G7080048889, G7776669727, G7786355547
OpenAlex ID: W7211955838