Cell Type-Specific Hormonal Signaling Configures Hypothalamic Circuits for Parenting

Parenting behavior emerges from hormonally sensitive circuits, but how distinct circuit components are affected by, and contribute to, sex and state dependent changes in infant caregiving remains unclear. Using cell type-specific approaches, we characterized two circuit nodes that are differentially configured by hormones to modulate infant-evoked behavior. An excitatory neuronal population in the anteroventral periventricular nucleus is only active in lactating mothers, increases virgin female caregiving when artificially stimulated and confers oxytocin sensitivity in mothers through a prolactin--STAT5b pathway. These neurons function upstream of another preoptic area population involved in male and female parenting, thus boosting caregiving by mothers. By contrast, androgen signaling in the latter preoptic population reshapes their intrinsic properties to promote pup-directed aggression, revealing cell type-specific tuning of social behavior circuits.

育儿行为源自激素敏感的神经环路，但目前学界尚未明确，不同的环路组分如何受到幼崽抚育行为中的性别与状态依赖变化的影响，又如何参与这类变化的调控。本研究采用细胞类型特异性方法，鉴定出两个被激素差异化调控以调节幼崽诱发行为的环路节点。前腹侧室周核（anteroventral periventricular nucleus）内的一群兴奋性神经元仅在泌乳母亲中激活；人工激活该神经元群体可提升未交配雌性的幼崽抚育行为，并通过催乳素-STAT5b信号通路赋予泌乳母亲催产素敏感性。这些神经元作为视前区（preoptic area）另一参与雌雄亲代抚育行为的神经元群体的上游发挥功能，从而增强母亲的幼崽抚育行为。与之相反，该视前区神经元群体中的雄激素信号通路会重塑其内在特性，以促进幼崽指向性攻击行为，这揭示了社会行为环路的细胞类型特异性调控机制。