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：
10586020
负责人：
Nancy Padilla Coreano
金额：
$ 24.9万
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 2025-03-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10586020
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.

项目概要社交缺陷在精神疾病中很常见，可用的治疗方法很有限。我们缺乏基本的关于大脑如何控制社交行为的知识使得开发社交疗法具有挑战性赤字。对于许多动物物种来说，社会等级决定了行为的许多方面，例如获得食物的机会资源和抗压能力。社会地位较高的人通常在社交活动中获胜的几率更高冲突（例如食物竞争）并表现出更多的竞争行为；集体性被称为支配性行为。跨物种证据表明内侧前额叶皮层 (mPFC) 在社会主导地位。然而，mPFC 究竟如何编码社会等级以及 mPFC 输入和输出是否有助于支配行为尚不清楚。多项研究表明，腹侧海马 (vHPC) 社交记忆是必需的，最近的一项研究表明，这一作用涉及 vHPC 对 mPFC 的输入。此外，初步数据表明，从 mPFC 到下丘脑外侧 (LH) 的投影调节社会支配行为。这些发现与文献相结合提出了一个模型，其中 mPFC 从 vHPC 接收社交记忆信息，并通过调节 LH 来指导社交行为 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由于现有的社会测定缺乏试验，因此受到用于表征小鼠社会行为的工具的限制统计能力和社会行为的常见测量所需的结构很简单（例如嗅探）。克服这一挑战需要开发一种基于试验的社会竞争测定法，让小鼠进行竞争与笼中的同伴进行对抗，以获得由声音表示的奖励。由于其试验结构，该测定法有利于社会行为的量化以及随后社会支配地位的神经相关因素的识别。在此测定中，占主导地位的小鼠在试验中赢得了大部分奖励，占据了奖励端口并取代了小鼠比下属更频繁地从奖励端口获得奖励。机器学习方法将用于分析在竞争分析中，不同社会等级的行为差异。利用这种与行为学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检验三方 vHPC-mPFC-LH 电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主导地位提供一种新方法，并将进一步加深我们对社会主导地位如何发挥作用的理解。 mPFC 的分布式电路调节社会行为。此外，查明潜在的神经回路社交行为将有助于确定精神疾病社交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剖析工具，这对于候选人成为社会专家至关重要神经科学并开始成功的独立研究计划。