Intraspecific chemosignals in the main olfactory system

主嗅觉系统中的种内化学信号

基本信息

批准号：
8246439
负责人：
WEIHONG LIN
金额：
$ 35.01万
依托单位：
UNIVERSITY OF MARYLAND BALTIMORE COUNTY
依托单位国家：
美国
项目类别：
财政年份：
2008
资助国家：
美国
起止时间：
2008-04-01 至 2014-03-31
项目状态：
已结题

项目摘要

DESCRIPTION (provided by applicant): Olfactory perception of intraspecific chemosignals provides sensory information about social and sexual status, genetic makeup, and species identity. In this proposal we describe experiments to investigate activities induced by these chemosignals and their underlying transduction mechanisms. Previously we have shown that the main olfactory system employs both cAMP- and phospholipase C- mediated pathways in pheromone signaling. Genetic knockout of the cyclic nucleotide-gated channel subunit 2 (CNGA2), which eliminates the cAMP signaling, does not eliminate pheromone-induced activation. In our preliminary study, we find that a novel signaling component, Transient Receptor Potential channel M5 (TRPM5), is present in a subset of mouse mature OSNs involved in olfactory signaling of pheromones and urinary components. Knockout of both CNGA2 and TRPM5 results in profound aberration in the main olfactory epithelium and bulbs, indicating the functional importance of TRPM5 in olfactory signaling. We hypothesize that TRPM5 is involved in signaling of intraspecific chemical cues in the main olfactory system. The proposed experiments fall into 3 aims. 1) We will test whether functional TRPM5 is crucial for intraspecific signal-evoked glomerular activation patterns. We will examine intraspecific chemosignals-induced activation in olfactory bulbs use immunolabeling of Fos protein as a neuronal activation marker and construct glomerular activation maps using a glomerular mapping program. We will then determine whether activated glomeruli receive input from the TRPM5-expressing OSNs, and whether knockout of TRPM5 alters the activation patterns. 2) We will test whether TRPM5-expressing OSNs provide sensory input to sustain tyrosine hydroxylase activity found in single CNGA2 knockout mice and whether double- knockouts of both CNGA2 and TRPM5 result in abnormality and neuronal death in the main olfactory system using anatomical and immunocytochemical approaches. 3) We will test whether TRPM5 is involved in signal transduction of intraspecific chemosignals in OSNs. We will characterize electrical and Ca2+ responses to pheromones and urine components in OSNs from TRPM5-GFP, TRPM5 knockout-GFP, CNGA2 knockout-TRPM5GFP mice and determine the functions of TRPM5 and associated pathways using Ca2+ imaging and electrophysiological recording methods. Taken together, the proposed studies will provide fundamental knowledge on signaling processing of intraspecific chemical cues and functional roles of TRPM5 in the main olfactory system. PUBLIC HEALTH RELEVANCE: In this application, we propose to investigate olfactory signaling mechanisms and the abnormality resulted from dysfunction of ion channels in the olfactory epithelium. Olfactory deficits are known to associate with aging and diseases. Our studies will provide knowledge ultimately useful for clinical treatment of olfactory dysfunctions.

描述（由申请人提供）：种内化学信号的嗅觉感知提供了有关社会和性状况，基因组成和物种认同的感官信息。在此提案中，我们描述了研究这些化学信号及其潜在转导机制引起的活动的实验。以前，我们已经表明，主要嗅觉系统在信息素信号传导中采用cAMP和磷脂酶C-介导的途径。消除cAMP信号传导的环状核苷酸门控通道亚基2（CNGA2）的遗传敲除不会消除信息素诱导的激活。在我们的初步研究中，我们发现一种新型的信号传导成分，瞬态受体电位通道M5（TRPM5）存在于与信息素和尿成分的嗅觉信号相关的小鼠成熟OSN的子集中。 CNGA2和TRPM5的敲除导致主要嗅觉上皮和灯泡的严重像差，表明TRPM5在嗅觉信号中的功能重要性。我们假设TRPM5参与主要嗅觉系统中种内化学提示的信号。提出的实验属于3个目标。 1）我们将测试功能性TRPM5是否对于种内信号引起的肾小球激活模式至关重要。我们将使用FOS蛋白作为神经元激活标记物的免疫标记来检查种内化学信号诱导的激活，并使用肾小球映射程序构建肾小球激活图。然后，我们将确定激活的glomeruli是否从表达TRPM5的OSN接收输入，以及TRPM5的敲除是否会改变激活模式。 2）我们将测试表达TRPM5的OSN是否提供感官输入，以维持单个CNGA2敲除小鼠中发现酪氨酸羟化酶活性，以及CNGA2和TRPM5的双重基因敲除是否会导致使用解剖学和免疫学和免疫细胞学方法的主要嗅觉系统中的异常和神经元死亡。 3）我们将测试TRPM5是否参与OSN中种内化学信号的信号转导。我们将表征来自TRPM5-GFP，TRPM5敲除GFP，CNGA2敲除TRPM5GFP小鼠的OSN中对信息素和尿液成分的电气和Ca2+响应，并使用CA2+成像和电学物理学记录方法来确定TRPM5和相关途径的功能。综上所述，拟议的研究将提供有关种内化学提示的信号处理和TRPM5在主要嗅觉系统中的功能作用的基本知识。公共卫生相关性：在此应用中，我们建议研究嗅觉信号传导机制和异常是由嗅觉上皮中离子通道功能障碍引起的。嗅觉缺陷已知与衰老和疾病有关。我们的研究将提供最终可用于嗅觉功能障碍的临床治疗的知识。

项目成果

期刊论文数量（7）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Diverse populations of intrinsic cholinergic interneurons in the mouse olfactory bulb.

DOI：
10.1016/j.neuroscience.2012.04.024
发表时间：
2012-06-28
期刊：
NEUROSCIENCE
影响因子：
3.3
作者：
Krosnowski, K.;Ashby, S.;Sathyanesan, A.;Luo, W.;Ogura, T.;Lin, W.
通讯作者：
Lin, W.

Skn-1a/Pou2f3 is required for the generation of Trpm5-expressing microvillous cells in the mouse main olfactory epithelium.

DOI：
10.1186/1471-2202-15-13
发表时间：
2014-01-16
期刊：
BMC neuroscience
影响因子：
2.4
作者：
Yamaguchi T;Yamashita J;Ohmoto M;Aoudé I;Ogura T;Luo W;Bachmanov AA;Lin W;Matsumoto I;Hirota J
通讯作者：
Hirota J

Dichotomous Distribution of Putative Cholinergic Interneurons in Mouse Accessory Olfactory Bulb.