All animals can perform certain survival behaviors without prior experience, suggesting a “hard wiring” of underlying neural circuits. Experience, however, can alter the expression of innate behaviors. Where in the brain and how such plasticity occurs remains largely unknown. Previous studies have established the phenomenon of “aggression training,” in which the repeated experience of winning successive aggressive encounters across multiple days leads to increased aggressiveness. Here, we show that this procedure also leads to long-term potentiation (LTP) at an excitatory synapse, derived from the posteromedial part of the amygdalohippocampal area (AHiPM), onto estrogen receptor 1-expressing (Esr1⁺) neurons in the ventrolateral subdivision of the ventromedial hypothalamus (VMHvl). We demonstrate further that the optogenetic induction of such LTP in vivo facilitates, while optogenetic long-term depression (LTD) diminishes, the behavioral effect of aggression training, implying a causal role for potentiation at AHiPM→VMHvl^Esr1 synapses in mediating the effect of this training. Interestingly, ∼25% of inbred C57BL/6 mice fail to respond to aggression training. We show that these individual differences are correlated both with lower levels of testosterone, relative to mice that respond to such training, and with a failure to exhibit LTP after aggression training. Administration of exogenous testosterone to such nonaggressive mice restores both behavioral and physiological plasticity. Together, these findings reveal that LTP at a hypothalamic circuit node mediates a form of experience-dependent plasticity in an innate social behavior, and a potential hormone-dependent basis for individual differences in such plasticity among genetically identical mice.

所有动物都可以在没有事先经验的情况下执行某些生存行为，这表明潜在的神经回路“硬连线”。但是，经验会改变先天行为的表达。大脑中的何处以及这种可塑性如何发生仍然未知。先前的研究已经建立了“攻击性训练”现象，在这种现象中，屡屡赢得连续数次侵略性战斗的反复经验会导致攻击性增强。在这里，我们表明，该程序还导致兴奋性突触的长期增强（LTP），该兴奋性突触来自杏仁核海马区（AHiPM）的后内侧部分，表达到雌激素受体1（Esr1 ⁺）腹侧下丘脑（VMHvl）腹侧细分中的神经元。我们进一步证明，在体内这种LTP的光遗传诱导促进，而光遗传长期抑郁症（LTD）减少，侵略性训练的行为效果，暗示在AHiPM→VMHvl ^Esr1增强的因果作用突触介导这种训练的效果。有趣的是，约25％的近交C57BL / 6小鼠对攻击性训练没有反应。我们表明，相对于对这种训练有反应的小鼠，这些个体差异既与较低水平的睾丸激素相关，又与攻击性训练后未能表现出LTP相关。对这种非攻击性小鼠施用外源性睾酮可恢复行为和生理可塑性。总之，这些发现表明，下丘脑回路节点处的LTP在先天社会行为中介导了一种形式的经验依赖性可塑性，并且是遗传上相同的小鼠之间这种可塑性的个体差异的潜在激素依赖性基础。