TrpM5 characterizes a main olfactory projection to the medial amygdala

描述（由申请人提供）：嗅觉是动物用来收集外部环境信息的一种重要的化学感觉方式。嗅觉系统调节食物定位、配偶选择、捕食者躲避和亲子互动等行为。最初，人们认为主嗅觉系统（MOS）传达关于“一般”气味的信息，而副嗅觉系统（AOS）则对“社会相关”气味（半化学物质）做出反应。然而，最近的发现表明这种分类不再合适。在包括小鼠在内的大多数陆生脊椎动物中，MOS的一部分与AOS并行工作，将有关半化学物质的气味信息传递到内侧杏仁核（MeA）。MeA是位于内侧颞叶的一组核，在许多社会相关行为中起着至关重要的作用。MeA与下丘脑有广泛的相互联系，因此对动物的激素状态有重大影响。了解MOS和AOS通路处理/传递符号化学气味的机制是理解这些信息流如何被更高的大脑结构（即MeA）整合并驱动最终行为的关键。最近的研究表明，那些表达瞬时受体电位通道（TrpM5）并投射到腹侧MOB的纤毛osn可以检测到符号化学信息。腹侧主嗅球（MOB）中的二尖瓣细胞亚群向腹侧主嗅球发送轴突。目前的项目旨在表征trpm5表达受体神经元作为雄性小鼠从MOS到MeA的神经通路的初始组成部分。拟议的项目将利用分子和生化技术来测试表达trpm5的osn是否将有关半化学物质的信息传递给MOB中投射到MeA的二尖瓣细胞亚群。TrpM5对这一途径的功能贡献也将被测量。具体目的如下：1)测试投射到内侧杏仁核的MOB的二尖瓣细胞是否优先接受TrpM5阳性肾小球的输入；2)测试TrpM5是否在参与向MeA传递信号化学气味信息的MOS神经通路的功能中是充分和必要的。从所提出的实验中获得的结果将有助于理解MOS如何处理与社会相关的气味。这些发现对于理解缺乏功能性AOS的物种（例如人类）如何仍然可以检测和响应社会气味线索非常重要。

DESCRIPTION (provided by applicant): Olfaction is a critical chemosensory modality used by animals to gather information concerning the external environment. The olfactory system mediates behaviors such as food localization, mate selection, predator avoidance and parent-offspring interactions. Initially, it was believed that the main olfactory system (MOS) conveyed information regarding 'general' odorants while the accessory olfactory system (AOS) responded to 'socially related' ones (semiochemicals). However, recent discoveries suggest that this classification is no longer appropriate. In most terrestrial vertebrates including mice, a portion of the MOS works in parallel with the AOS to convey odorant information regarding semiochemicals to the medial amygdala (MeA). The MeA is a collection of nuclei located in the medial temporal lobe previously shown to be essential in many socially relevant behaviors. The MeA has extensive interconnections with the hypothalamus and therefore exerts significant influence upon the hormonal state of the animal. Knowledge of the mechanisms that both MOS and AOS pathways employ to process/transmit semiochemical odorants is key to understanding how these streams of information are integrated by higher brain structures (i.e. MeA) which drive the resulting behavior. Recent investigations suggest that semiochemical information is detected by those ciliated OSNs that express the transient receptor potential channel (TrpM5) and which project to the ventral MOB. A subpopulation of mitral cells in the ventral main olfactory bulb (MOB) sends axons to the MeA. The current project is aimed at characterizing TrpM5-expressing receptor neurons as the initial components of a neural pathway projecting from the MOS to the MeA in male mice. The proposed project will utilize molecular and biochemical techniques to test whether TrpM5-expressing OSNs transmit information regarding semiochemicals to the subset of mitral cells in the MOB that project to the MeA. The functional contribution of TrpM5 to this pathway will also be measured. The Specific Aims are the following: 1) to test whether those Mitral cells of the MOB that project to the medial amygdala, preferentially receive input from TrpM5-positive glomeruli, and 2) to test whether TrpM5 is both sufficient and necessary for functionality of the MOS neural pathway involved in transmission of semiochemical odorant information to the MeA. The results obtained from the proposed experiments will aid in understanding how the MOS processes socially-related odors. These findings will be important in understanding how species (e.g. humans) that lack a functional AOS can still detect and respond to social odor cues.