Sensory processing of social and defensive chemosignals

描述(申请人提供)：这个项目的目标是研究在许多物种中，社交化学信号是如何被犁鼻回路处理的，引导社交互动所必需的信号依赖于信息素的发射和检测。啮齿动物强烈依赖犁鼻系统来检测这些线索，并指导预先设定好的遗传程序、社交和防御行为。我们和其他人最近在了解犁鼻器(VNO)化学感觉检测的分子和细胞基础以及显示其主要目标副嗅球(AOB)的复杂活动模式方面取得了重大进展。然而，下游脑区进行的信息处理是为了引起先天的行为反应。编码与行为相关的信号还没有被发现。这个项目利用新的电生理学、遗传学和光遗传学方法来确定来自(MEA)的单位如何将社会和防御感觉线索转换为与行为相关的信号。在参与诱发不同行为反应的AOB和下丘脑不同核团之间的犁鼻-感觉运动转换中，MeA占有重要地位。杏仁内侧核拟议的实验将解决1-MEA如何处理来自AOB的复杂感觉表征，以便将反映检测到的线索的行为意义的信息传递到下丘脑的中心。2-MEA中不同遗传定义的神经元群体的感觉表征，更具体地说，表达芳香酶(AR)或促甲状腺激素释放激素(TRH)的两个互补神经元群体的反应，这两个神经元群体分别位于MEA的不同区域，据报道分别驱动交配和防御行为。3-使用转基因小鼠品系和光遗传工具，使与检测到捕食者以及雄性和雌性同种动物相对应的离散受体群体能够激活，基本的VNO信号对整个大脑的神经元激活的贡献。在人类中，社会认知缺陷是自闭症和精神分裂症等知之甚少、令人衰弱的精神障碍的核心。由于它们在环境线索的编码和处理中的中心作用导致适当的行为反应，这些研究中发现的社会和防御识别的神经原理在很大程度上适用于整个动物界。因此，我们的发现将为精神障碍的诊断和治疗提供信息，在精神障碍中，社交和感觉交流受到损害。

DESCRIPTION (provided by applicant): The goal of this project is to investigate how social chemosignals are processed by vomeronasal circuits in many species, the signals essential for guiding social interactions rely on the emission and detection of pheromones. Rodents strongly rely on the vomeronasal system to detect these cues and guide genetically pre-programmed social and defensive behaviors. We, and others, have recently made significant progress in understanding the molecular and celular basis of chemosensory detection by the vomeronasal organ (VNO) and in visualizing complex patterns of activity by its primary target, the accessory olfactory bulb (AOB). However, the information processing performed by downstream brain areas in order to elicit innate behavioral responses. encode behaviorally relevant signals has not yet been uncovered. This project draws on novel electrophysiological, genetic and optogenetic approaches to determine how units from the (MeA) transform social and defensive sensory cues into behavioraly relevant signals. The MeA occupies a critical position in the vomeronasal-sensorimotor transformation between the AOB and distinct nuclei of the hypothalamus that are involved in eliciting distinct behavioral responses. medial amydgala Proposed experiments will address 1- how the MeA processes the complex sensory representation from the AOB, in order to convey information reflecting the behavioral significance of the detected cues to centers in the hypothalamus. 2- the sensory representation of distinct genetically defined populations of neurons in the MeA, and more specifically the responses of two complementary populations of neurons expresing either the enzyme aromatase (Ar) or thyrotropin-releasing hormone (TRH that are located in distinct areas of the MeA reported to drive mating and defensive behaviors, respectively. 3- the contribution of elementary VNO signals to neuronal activation across the brain using transgenic mouse lines and optogenetic tools that enable the activation of discrete receptor populations corresponding to the detection of predators, as well as male and female conspecifics. In humans, defects in social recognition are the core of poorly understood and debilitating mental disorders such as autism and schizophrenia. Because of their central role in the coding and processing of environmental cues leading to appropriate behavioral responses, the neural principles of social and defensive recognition uncovered in these studies are largely applicable throughout the animal kingdom. Thus, our findings will inform the diagnosis and treatment of mental disorders, in which social and sensory communications are impaired.