Mice lacking acid-sensing ion channel 2 in the medial prefrontal cortex exhibit social dominance

作者：Boren Lin, Zhen Jin, Kyung Ah Park, Qian Ge, Kritika Singh, William G. Ryan, Ali Sajid Imami, Farzaneh Naghavi, Olivia A. Miller, Saira Khan, Hui Lü, Robert E. McCullumsmith, Jianyang Du · 发表于：Science Advances · 年份：2024 · DOI：10.1126/sciadv.adn7573 · 被引用次数：3 · 研究领域：Ion Transport and Channel Regulation、Sleep and Wakefulness Research、Neuroendocrine regulation and behavior

Social dominance is essential for maintaining a stable society and has both positive and negative impacts on social animals, including humans. However, the regulatory mechanisms governing social dominance, as well as the crucial regulators and biomarkers involved, remain poorly understood. We discover that mice lacking acid-sensing ion channel 2 (ASIC2) exhibit persistently higher social dominance than their wild-type cagemates. Conversely, overexpression of ASIC2 in the medial prefrontal cortex reverses the dominance hierarchy observed in ASIC2 knockout ( Asic2 −/− ) mice. Asic2 −/− neurons exhibit increased synaptic transmission and plasticity, potentially mediated by protein kinase A signaling pathway. Furthermore, ASIC2 plays distinct functional roles in excitatory and inhibitory neurons, thereby modulating the balance of neuronal activities underlying social dominance behaviors—a phenomenon suggestive of a cell subtype–specific mechanism. This research lays the groundwork for understanding the mechanisms of social dominance, offering potential insights for managing social disorders, such as depression and anxiety.