Acetylcholine drives astrocytic JAK2-STAT3 signaling to modulate male-to-female approach behavior
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…
Astrocytes, known for their role in regulating neural circuits and behavior, hold a key position in linking external stimuli to long-term transcriptional programs. However, the extent of astrocyte transcription factor-based cascades remains unclear. This study reveals that the JAK2-STAT3 signaling pathway is crucial in modulating male-to-female social behavior.
In response to estrus females, male mice exhibit a rapid and specific activation of STAT3 signaling in their ventral hippocampal astrocytes. This induction is not a result of traditional cytokine signaling, but rather through septo-hippocampal cholinergic inputs acting via 7 nicotinic acetylcholine receptors (7nAChR). The astrocytic 7nAChR-JAK2-STAT3 signaling subsequently influences vCA1 pyramidal neuron activity and is essential for context-appropriate male approach behavior.
This discovery uncovers an unforeseen cellular pathway that integrates neuromodulatory inputs and transcription factor-based signaling to shape male behavioral responses based on female receptivity.
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