Selective Vulnerability of Parvocellular Oxytocin Neurons in Social Dysfunction

Selective vulnerability offers a conceptual framework for understanding neurodegenerative disorders, such as Parkinsons disease, where specific neuronal types are selectively affected while adjacent ones are spared. The applicability of this framework to neurodevelopmental disorders remains uncertain, particularly those characterized by atypical social behaviors such as autism spectrum disorder. Here, employing a single-cell transcriptome analysis in mice, we show that an embryonic disturbance known to induce social dysfunction preferentially impairs gene expressions crucial for neural functions in parvocellular oxytocin (OT) neurons--a subtype linked to social rewards--while neighboring cell types experience a lesser impact. Chemogenetic stimulation of OT neurons at the neonatal stage ameliorated social deficits in early adulthood, concurrent with a cell-type-specific sustained recovery of the pivotal gene expressions within parvocellular OT neurons. Collectively, our data shed light on the transcriptomic selective vulnerability within the hypothalamic social behavioral center and provide a potential therapeutic target through specific neonatal neurostimulation.