Department of Neurology of Second Affiliated Hospital and School of Brain Science and Brain Medicine, Zhejiang University School of Medicine, Hangzhou 310058, China; Liangzhu Laboratory, MOE Frontier Science Center for Brain Science & Brain-Machine Integration, State Key Laboratory of Brain-Machine Intelligence, Zhejiang University, Hangzhou 311121, China; NHC and CAMS Key Laboratory of Medical Neurobiology, Zhejiang University, Hangzhou 310058, China.
Westlake Laboratory of Life Sciences and Biomedicine, Institute of Biology, School of Life Sciences, Westlake Institute for Advanced Study, Westlake University, Hangzhou 310024, China.
Neuron. 2024 Sep 25;112(18):3176-3191.e7. doi: 10.1016/j.neuron.2024.06.022. Epub 2024 Jul 16.
Male animals often display higher levels of aggression than females. However, the neural circuitry mechanisms underlying this sexually dimorphic aggression remain elusive. Here, we identify a hypothalamic-amygdala circuit that mediates male-biased aggression in mice. Specifically, the ventrolateral part of the ventromedial hypothalamus (VMHvl), a sexually dimorphic region associated with eliciting male-biased aggression, projects densely to the posterior substantia innominata (pSI), an area that promotes similar levels of attack in both sexes of mice. Although the VMHvl innervates the pSI unidirectionally through both excitatory and inhibitory connections, it is the excitatory VMHvl-pSI projections that are strengthened in males to promote aggression, whereas the inhibitory connections that reduce aggressive behavior are strengthened in females. Consequently, the convergent hypothalamic input onto the pSI leads to heightened pSI activity in males, resulting in male-biased aggression. Our findings reveal a sexually distinct excitation-inhibition balance of a hypothalamic-amygdala circuit that underlies sexually dimorphic aggression.
雄性动物通常比雌性动物表现出更高水平的攻击性。然而，这种性别二态性攻击的神经回路机制仍然难以捉摸。在这里，我们确定了一个下丘脑-杏仁核回路，该回路介导了雄性偏向的攻击。具体来说，腹内侧下丘脑的腹外侧部分（VMHvl）是一个与引发雄性偏向攻击相关的性别二态区域，它密集投射到后侧无名质（pSI），该区域促进雌雄小鼠攻击水平相似。尽管 VMHvl 通过兴奋性和抑制性连接单向支配 pSI，但在雄性中增强的是兴奋性 VMHvl-pSI 投射，以促进攻击，而减少攻击行为的抑制性连接在雌性中增强。因此，汇聚到 pSI 的下丘脑输入导致雄性 pSI 活性升高，从而导致雄性偏向的攻击。我们的发现揭示了一个下丘脑-杏仁核回路的性别独特的兴奋-抑制平衡，该平衡是性别二态性攻击的基础。
