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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

基本信息

批准号：
10767404
负责人：
Nancy Padilla Coreano
金额：
--
依托单位：
UNIVERSITY OF FLORIDA
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-04-01 至 2024-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10767404
关键词：
Affect Agonistic Behavior Animals Behavior Behavioral Behavioral Assay Bilateral Biological Assay Calcium Cells Data Dissection Electrophysiology (science)Food Frequencies Glutamates Goals Hippocampus Human Hypothalamic structure Image Individual Investigation Knowledge Lateral Literature Machine Learning Measurement Medial Memory Mental disorders Mentors Methods Modeling Motivation Mus Opsin Optics Output Partner in relationship 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 cell cortex in vivo in vivo imaging mind control neural neural circuit neural correlate nonhuman primate novel novel strategies optogenetics programs recruit redshift resilience social social competition social deficits social influence social interventions social neuroscience tool training opportunity unsupervised learning wireless

项目摘要

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障碍中很常见，可用的治疗方法也很有限。我们对基础设施的缺乏关于大脑如何控制社交行为的知识使开发社交疗法变得具有挑战性赤字。对于许多动物物种来说，社会地位决定了行为的许多方面，例如获得资源和对压力的适应能力。社会地位较高的个人通常在社交活动中获胜的几率更大冲突(例如食物竞争)，并表现出更多的争斗行为；集体被称为优势行为。跨物种证据表明，内侧前额叶皮质(MPFC)在社会支配地位。然而，mPFC究竟如何编码社会等级以及哪些mPFC输入和输出对支配行为的贡献是未知的。多项研究表明，腹侧海马(VHPC) 这是社会记忆所必需的，最近的一项研究表明，这一角色涉及vHPC对mPFC的输入。此外，初步数据表明，从mPFC到外侧下丘脑(Lh)的投射。调节社会支配行为。这些发现结合文献提出了一种模型，在该模型中 MPFC接收来自vHPC的社会记忆信息，并通过对LH值的调制来引导社会行为 GABA能和谷氨酸能亚群。在揭示社会行为的神经关联方面取得了进展受到了用来描述老鼠社交行为的工具的限制，因为现有的社交测试缺乏试验- 统计权力所需的结构和社会行为的常见衡量标准过于简单化(例如，嗅探)。克服这一挑战需要开发一种以试验为基础的社会竞争分析方法，在这种方法中，老鼠可以进行竞争反对笼子，为了通过语气发出的奖励。由于其试验结构，本试验有助于对社会行为进行量化，并随后确定与社会支配地位相关的神经。在这个实验中，优势小鼠在试验中赢得了大部分奖励，占据了奖励端口，取代了小鼠。从奖励港来的次数比从下属那里多。将使用机器学习方法来分析在竞争分析期间，社会等级之间的行为差异。利用这一与行为相关的社会竞争分析、电路操作、体内神经记录方法和机器学习允许测试vHPC-mPFC-LH三方回路编码社会支配地位的假设。总而言之，这研究将为研究社会支配地位提供一种新的方法，并将加深我们对 MPFC的分布回路调节社会行为。此外，找出潜在的神经回路社会行为将有助于确定精神障碍中社会缺陷的潜在治疗方法。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，这是候选人成为社会专家所必需的并启动一项成功的独立研究计划。