Studying how the hippocampal-prefrontal-hypothalamic circuit encodes social dominance

研究海马-前额叶-下丘脑回路如何编码社会主导地位

• 批准号: 10041744
• 负责人: Nancy Padilla Coreano
• 金额: $ 12.34万
• 依托单位: SALK INSTITUTE FOR BIOLOGICAL STUDIES
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-06-01 至 2022-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10041744
• 关键词: Affect; Agonistic Behavior; Animals; Behavior; Behavioral; Behavioral Assay; Bilateral; Biological Assay; Calcium; Cells; Conflict (Psychology); Data; Dissection; Electrophysiology (science); Food; Frequencies; Glutamates; Goals; Hippocampus (Brain); Human; Hypothalamic structure; Image; Individual; Investigation; Knowledge; Lateral; Literature; Machine Learning; Measurement; Medial; Memory; Mental disorders; Mentors; Methods; Modeling; Motivation; Mus; Opsin; Optics; Output; Pathway Analysis; Phase; Play; Prefrontal Cortex; Probability; Research; Resources; Rewards; Rodent; Role; Signal Transduction; Site; Social Behavior; Social Dominance; Social Environment; Social Interaction; Stress; Structure; Techniques; Testing; Therapeutic; Time; Training; Tube; Wireless Technology; base; cell cortex; in vivo; in vivo imaging; mind control; neural circuit; neural correlate; nonhuman primate; novel; novel strategies; optogenetics; programs; recruit; redshift; relating to nervous system; resilience; social; social competition; social deficits; social interventions; social neuroscience; tool; training opportunity; unsupervised learning

Project Summary Social deficits are common in psychiatric disorders and available treatments are limited. Our lack of basic knowledge on how the brain controls social behaviors makes it challenging to develop therapeutics for social deficits. For numerous animal species, social rank dictates many aspects of behavior, such as access to resources and resilience to stress. Individuals with higher social rank typically win more often during social conflicts (e.g. food competition) and show more agonistic behaviors; collectivity referred to as dominance behaviors. Cross-species evidence suggests that the medial prefrontal cortex (mPFC) plays an important role in social dominance. However, exactly how the mPFC encodes social rank and which mPFC inputs and outputs contribute to dominance behaviors is unknown. Multiple studies show that the ventral hippocampus (vHPC) is necessary for social memory, and more recently, a study showed that this role involves vHPC input to the mPFC. Furthermore, preliminary data suggest that the projection from the mPFC to the lateral hypothalamus (LH) modulates social dominance behavior. These findings in combination with the literature suggest a model in which the mPFC receives social memory information from the vHPC and guides social behaviors via modulation of LH GABAergic and glutamatergic subpopulations. Progress in uncovering neural correlates of social behavior has been limited by the tools used to characterize murine social behavior, since existing social assays lack trial- structure needed for statistical power and common measurements of social behavior are simplistic (e.g. sniffing). Overcoming this challenge required developing a trial-based social competition assay in which mice compete against cagemates for a reward signaled by a tone. Due to its trial structure, this assay facilitates the quantification of social behaviors and subsequently the identification of neural correlates for social dominance. In this assay, dominant mice win most of the rewards across trials, occupy the reward port and displace mice from the reward port more often than subordinates. Machine learning approaches will be used to profile the behavioral differences seen across social rank during the competition assay. Utilizing this ethologically relevant social competition assay, circuit manipulations, in vivo neural recording methods and machine learning allows testing the hypothesis that the tripartite vHPC-mPFC-LH circuit encodes social dominance. Altogether, this research will provide a new approach to study social dominance and will further our understanding of how the distributed circuits of the mPFC modulate social behavior. Furthermore, pinpointing the neural circuits underlying social behaviors will facilitate identification of potential therapeutics for social deficits in psychiatric disorders. Finally, completion of this research will provide training opportunities in statistical approaches for behavioral analysis and new circuit dissection tools, which are essential for the candidate to become an expert in social neuroscience and to start a successful independent research program.

项目摘要 社会缺陷在精神疾病中很常见，可用治疗量受到限制。我们缺乏基本 关于大脑如何控制社会行为的知识使得为社会发展治疗学挑战 缺陷。对于众多动物物种，社会等级决定了行为的许多方面，例如进入 资源和压力的韧性。社会等级较高的人通常在社会期间赢得更多的胜利 冲突（例如食品竞争）并表现出更多的激动行为；集体称为主导 行为。跨物种证据表明，内侧前额叶皮层（MPFC）在 社会主导地位。但是，MPFC准确地编码社交等级以及哪些MPFC输入和输出 为主导行为做出贡献是未知的。多项研究表明，腹侧海马（VHPC）为 社交记忆所需的，最近的一项研究表明，该作用涉及MPFC的VHPC输入。 此外，初步数据表明，MPFC对下丘脑（LH）的投影 调节社会统治行为。这些发现与文献相结合，提出了一个模型 MPFC从VHPC接收社交记忆信息，并通过调节LH指导社交行为 GABA能和谷氨酸能亚群。发现社会行为的神经相关性方面的进展已有 受到用来表征鼠社会行为的工具的限制，因为现有的社会测定缺乏试验 - 统计能力和社会行为的共同测量所需的结构很简单（例如嗅探）。 克服这一挑战需要开发基于试验的社会竞争测定法，其中小鼠竞争 反对卡吉特人，以表达语调的奖励。由于其试验结构，该测定有助于 量化社会行为，随后识别社会主导地位的神经相关性。 在此测定中，占主导地位的老鼠赢得了大部分的回报，占据了奖励端口并取代老鼠 从奖励港口比下属更多。机器学习方法将用于概括 竞争分析期间社会等级之间看到的行为差异。利用这种伦理学相关的 社会竞争测定，电路操作，体内神经记录方法和机器学习允许 测试三方VHPC-MPFC-LH电路编码社会优势的假设。总共，这个 研究将提供一种新的方法来研究社会主导地位，并将进一步了解 MPFC的分布式电路调节社会行为。此外，指出了下面的神经回路 社会行为将有助于识别精神疾病中社会缺陷的潜在治疗剂。 最后，这项研究的完成将为行为统计方法提供培训机会 分析和新的电路解剖工具，这对于候选人成为社会专家至关重要 神经科学并启动成功的独立研究计划。