Characterization of neural circuits mediating social behavior

介导社会行为的神经回路的表征

• 批准号: 7997576
• 负责人: Joseph Fossland Bergan
• 金额: $ 5.05万
• 依托单位: HARVARD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-06-01 至 2013-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7997576
• 关键词: Accessory Olfactory Bulbs; Amygdaloid structure; Aromatase; Aromatase Inhibitors; Behavior; Behavioral; Brain; Breast Cancer Treatment; Categories; Cell Nucleus; Collaborations; Cues; Data Analyses; Detection; Dorsal; Electrophysiology (science); Environment; Generations; Genetic; Medial; Mediating; Molecular; Molecular and Cellular Biology; Mus; Neurons; Partner in relationship; Pattern; Population; Production; Property; Research Personnel; Role; Sensory; Signal Transduction; Social Behavior; Staging; Stimulus; Vomeronasal Systems; Work; awake; information processing; insight; member; neural circuit; neuromechanism; public health relevance; relating to nervous system; reproductive; research study; response; segregation; skills; Accessory Olfactory Bulbs; Amygdaloid structure; Aromatase; Aromatase Inhibitors; Behavior; Behavioral; Brain; Breast Cancer Treatment; Categories; Cell Nucleus; Collaborations; Cues; Data Analyses; Detection; Dorsal; Electrophysiology (science); Environment; Generations; Genetic; Medial; Mediating; Molecular; Molecular and Cellular Biology; Mus; Neurons; Partner in relationship; Pattern; Population; Production; Property; Research Personnel; Role; Sensory; Signal Transduction; Social Behavior; Staging; Stimulus; Vomeronasal Systems; Work; awake; information processing; insight; member; neural circuit; neuromechanism; public health relevance; relating to nervous system; reproductive; research study; response; segregation; skills

DESCRIPTION (provided by applicant): The vomeronasal system (VNS) detects important chemosensory cues in the local environment and transforms these cues into adaptive social behaviors. Despite myriad advances in our understanding of the cellular and molecular biology of the VNS, several essential questions remain unexplored, in particular concerning the electrophysiological properties of higher nuclei in the VNS. The studies described in this proposal are aimed at identifying neural computations occurring in the medial amygdala (MEA) that are critical for the transduction of sensory cues and generation of social behavior. Several convincing lines of anatomical, molecular, pharmacological, and behavioral evidence indicate that MEA neurons represent a critical stage for information processing within the VNS. The MEA receives sensory input from the accessory olfactory bulb, and is reciprocally connected with a network of nuclei essential for the production or social behaviors. The MEA is segregated into regions with distinct genetic expression patterns that delineate important functional segregations. For example, the posterior dorsal MEA (MEApd) is important for the detection of reproductive stimuli, while the posterior ventral MEA (MEApv) is specialized to detect defensive stimuli. Aromatase-expressing neurons, found in the MEApd but not in the MEApv, are sexually dimorphic in number and projection pattern, and are thought to underlie VNS mediated sexually dimorphic behaviors. The work outlined in the proposal will be performed over the next three years. The principle investigator will conduct the vast majority of the described experiments and data analyses. However, several key components of these experiments will be conducted in collaboration with members of the Dulac lab having relevant skill sets. Each aim of this proposal employs recording electrophysiological responses in the MEA while stimulating the VNS with ethologically important stimuli. Stimuli were chosen to encompass broad categories such as predators, mates, sympatric competitors, and kin. The purpose of the first specific aim is to systematically determine patterns of chemosensory responses present in the MEA. The second aim extends these findings by assigning specific response patterns to genetically defined populations of MEA neurons. The third aim, investigates the role of the MEA in guiding social behavior using electrophysiology in awake mice. These complimentary experimental approaches will provide important insights into the neural mechanisms that detect chemosensory cues and produce essential social behaviors. PUBLIC HEALTH RELEVANCE: Since aromatase inhibitors are rapidly becoming a first-line treatment for breast cancer, it is important to understand the normal function of aromatase signaling in the brain. The functional characterization of aromatase expressing neurons will likely provide important insights for the beneficial treatment of breast cancer.

描述（由申请人提供）：Vomeronasal系统（VNS）检测到当地环境中的重要化学感知线索，并将这些线索转化为适应性的社会行为。尽管我们对VNS的细胞和分子生物学的理解有无数的进步，但仍未探索几个基本问​​题，特别是关于VNS中较高核的电生理特性。该提案中描述的研究旨在鉴定内侧杏仁核（MEA）中发生的神经计算，这些神经计算对于转导感觉线索和社会行为的产生至关重要。 解剖学，分子，药理和行为证据的几条令人信服的线条表明，MEA神经元是VNS内信息处理的关键阶段。 MEA从附属嗅球接收感官输入，并与对生产或社交行为必不可少的核网络相互联系。 MEA被隔离为具有不同遗传表达模式的区域，这些区域描绘了重要的功能分离。例如，后背MEA（MEAPD）对于检测生殖刺激很重要，而后腹侧MEA（MEAPV）专门用于检测防御性刺激。在MEAPD中发现但不是在MEAPV中发现的表达芳香酶的神经元，在数量和投影模式上是性二态性的，被认为是VNS介导的性二态行为的基础。 提案中概述的工作将在未来三年内进行。原则研究者将进行绝大多数描述的实验和数据分析。但是，这些实验的几个关键组成部分将与具有相关技能的DULAC实验室成员合作进行。 该提案的每个目的都采用记录在MEA中的电生理反应，同时用伦理上重要的刺激刺激VN。选择刺激以包括捕食者，伴侣，同胞竞争者和亲属等广泛类别。第一个具体目的的目的是系统地确定MEA中存在的化学感应响应的模式。第二个目标通过将特定的响应模式分配给MEA神经元的遗传定义群体，从而扩展了这些发现。第三个目的是研究MEA在清醒小鼠中使用电生理学指导社会行为的作用。这些免费的实验方法将为检测化学感知线索并产生基本社会行为的神经机制提供重要的见解。 公共卫生相关性：由于芳香酶抑制剂正迅速成为乳腺癌的一线治疗方法，因此了解大脑中芳香酶信号的正常功能很重要。表达神经元的芳香酶的功能表征可能会为乳腺癌的有益治疗提供重要的见解。