DEVELOPMENT OF SEXUALLY DIMORPHIC OLFACTORY GLOMERULI

脊椎动物和无脊椎动物的初级嗅觉神经丸都以突触肾小球排列为特征，每个突触肾小球处理有关气味刺激的特定属性的信息；但人们对这些引人注目的空间阵列是如何形成的知之甚少。在Manduca sexta蛾中，嗅觉神经包括64个在雄性和雌性中看起来相似的肾小球，以及两到三个专门的、容易识别的肾小球，这些肾小球是每一种性别所特有的，它们处理对繁殖很重要的气味信息。先前的实验已经证明，男性特有的一组特殊肾小球，包括招募女性目标神经元进入该回路。此外，即使从异常位置进入大脑，这些男性特有的轴突也能找到正确的目标位置。因此，Manduca的两性二态嗅觉系统提供了一个特殊的机会来研究嗅觉发育中的一个核心问题：什么细胞相互作用是肾小球阵列发育的基础。提出的项目解决了这个问题，有两个具体目标：(1)探索男性特异性嗅觉受体轴突在目标嗅觉神经中识别的“地址”方面，并确定这些轴突与特定目标神经元之间的突触相互作用是否构成了轴突在这些神经元中诱导的树突形态的基础；(2)确定一氧化氮（一种由嗅觉轴突发育释放的气体细胞间信号分子）在天线叶两性同构和两性异型肾小球发育中的作用。该项目利用飞蛾嗅觉系统的相对细胞简单性，并使用最先进的显微方法以及电生理、生化和分子生物学方法，有望为不易接近的哺乳动物嗅觉系统的发展提供见解。

Primary olfactory neuropils in both vertebrates and invertebrates are characterized by arrays of synaptic glomeruli, each of which processes information about particular attributes of odorous stimuli; but little is known about how these striking spatial arrays develop. In the moth Manduca sexta, the olfactory neuropil comprises 64 glomeruli that appear to be similar in males and females, and two to three specialized and easily recognizable glomeruli that are unique to each sex and that process information about odors important for reproduction. Previous experiments have demonstrated that male-specific group of specialized glomeruli, including recruitment of female target neurons into that circuitry. Furthermore, even if entering the brain from an abnormal position, those male-specific axons find the correct target site. Thus, the sexually dimorphic olfactory system of Manduca offers a special opportunity to investigate a central question in olfactory development: what cellular interactions underlie the development of the array of glomeruli. The proposed project addresses the question, with two specific aims: (1) to explore aspects of the "address" that male-specific olfactory receptor axons recognize in the target olfactory neuropil and to determine whether synaptic interactions between those axons and particular target neurons underlie the dendritic morphology that the axons induce in those neurons; and (2) to determine the role of nitric oxide, a gaseous intercellular signaling molecule which appears to be released by developing olfactory axons, in the development of both sexually isomorphic and sexually dimorphic glomeruli in the antennal lobe. The project, taking advantage of the relative cellular simplicity of the moth olfactory system, and using state-of-the-art microscopical methods in addition to electrophysiological, biochemical, and molecular biological approaches is expected to provide insights into the development of less accessible mammalian olfactory systems.