Mechanisms of experience-dependent plasticity in an innate social behavior circuit

项目摘要 许多社交行为，如防御和攻击，都是与生俱来的--不需要事先的经验 被表达出来，并可能被“硬连线”到神经回路。然而，有趣的是，这些“硬连线”行为 不同个体的表达方式不同，并且可以通过经验来改变。什么是神经回路和 支持如此灵活地表达先天行为的机制？腹外侧腹内侧 下丘脑(VMHvl)控制着包括攻击和社会防御在内的先天社会行为，但 VMHvl编码这些行为表达的个体差异，或者VMHvl可能如何调节 依赖经验的行为变化是不被理解的。一种暴露个人的体验 与生俱来的行为差异并导致攻击和防御的经验依赖性变化 行为是慢性社会失败应激(CDS)。镉诱导VMHv1活性的持续变化-但细胞- 这些转换涉及的类型、电路和机制尚不清楚。该提案将使用CDS 产生一系列的社会行为决定，并剖析细胞类型、回路和突触机制 使用多个层次的分析来协调这些决定。这包括个体的体内成像 神经元在CDS、电生理过程中VMHv1活性动态的表征 记录以揭示VMHvl回路中CDS的细胞和突触特征，以及体内的光发生 在行为过程中的操纵以扰乱VMHvl CDS的可塑性。这项建议在技术上具有重大意义 以及电路映射、体内记录、体内电路操作、细胞类型和输入方面的概念培训- 具体的突触可塑性，以及计算和定量分析方法。共同完成 这项研究将阐明发生的对VMHvl电路动力学的经验依赖的转换 在整个社会压力中，并将这些变化与压力结果的个体差异联系起来。 研究这些关系将提供对应力-塑性的潜在机制的洞察，这些机制为 对与压力相关的心理健康障碍的洞察。

Project Summary Many social behaviors, such as defense and aggression, are innate- requiring no prior experience to be expressed and presumably ‘hardwired’ into neural circuits. Interestingly, however, these ‘hardwired’ behaviors vary in expression among individuals and can be altered by experience. What are the neural circuits and mechanisms that support such flexible expression of innate behaviors? The ventrolateral, ventromedial hypothalamus (VMHvl) controls innate social behaviors including aggression and social defense, but whether VMHvl encodes individual differences in the expression of these behaviors, or how VMHvl may mediate experience-dependent behavioral changes is not understood. An experience that exposes individual differences in innate behavior and induces experience-dependent changes to aggression and defense behavior is chronic social defeat stress (CDS). CDS induces persistent changes to VMHvl activity- but the cell- types, circuits, and mechanisms involved in these transformations are unidentified. This proposal will use CDS to produce a range of social behavior decisions and dissect the cell-types, circuits, and synaptic mechanisms that mediate these decisions using multiple levels of analysis. This includes in-vivo imaging of individual neurons to characterize the activity dynamics of VMHvl throughout the course of CDS, electrophysiological recordings to uncover the cellular and synaptic signatures of CDS in VMHvl circuits, and in-vivo optogenetic manipulation during behavior to perturb VMHvl CDS-plasticity. This proposal constitutes significant technical and conceptual training in circuit-mapping, in-vivo recordings, in-vivo circuit manipulation, cell-type and input- specific synaptic plasticity, and computational and quantitative methods of analysis. Together, completion of this research will elucidate the experience-dependent transformations to VMHvl circuit dynamics that occur throughout social stress, and relate these transformations to individual differences in stress outcome. Examining these relationships will provide insight to the mechanisms underlying stress-plasticity, which provide insight to stress-related mental health disorders.