Spatial dynamics of cellular and molecular plasticity in the maternal and postpartum mouse brain

Pregnancy represents a critical window for neuroplasticity and maternal mental health, yet our understanding of the molecular and cellular mechanisms driving this neural adaptation remains incomplete. Here, we generated a spatially resolved transcriptomic atlas of the maternal mouse brain, integrating Slide-tags and MERFISH to profile nearly one million cells. We uncover widespread remodeling characterized by a striking divergence: neurons suppress metabolic and synaptic machinery, while non-neuronal cells activate homeostatic programs for angiogenesis and stress response. Spatially, we identify a transient neurovascular niche in the medial preoptic area (MPOA), where hormonally primed Lhx8+ neurons exhibit neurovascular coupling with endothelial cells, coinciding with upregulated VEGF signaling to support this behavioral hub. Finally, we map the cellular basis of peripartum psychiatric vulnerability, revealing that genetic risk for major depressive disorder is cell type- and stage-specific, converging onto cortical neurons specifically during their pregnancy-induced transcriptional suppression. This resource reveals the dynamic spatial architecture of the maternal brain and provides a molecular framework for understanding peripartum adaptation and disease risk.