DEVELOPMENT OF SEXUALLY DIMORPHIC OLFACTORY GLOMERULI

脊椎动物和无脊椎动物的初级嗅觉神经髓都以突触小球阵列为特征，每个突触小球处理关于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发展的知之甚少。在蛾Manduca sexta中，嗅神经球由雄性和雌性相似的小球和两到三个专门的、容易辨认的雄性和雌性特有的小球组成，这些小球处理有关气味的信息，这些信息对繁殖至关重要。以前的实验已经证明，男性特有的一组特化肾小球，包括招募女性靶神经元进入该回路。此外，即使从不正常的位置进入大脑，这些男性特有的轴突也会找到正确的目标位置。因此，Manduca的性二形态嗅觉系统为研究嗅觉发育中的一个中心问题提供了一个特殊的机会：什么细胞相互作用是肾小球阵列发育的基础。这个拟议的项目解决了这个问题，有两个具体的目标：(1)探索男性特有的嗅觉感受器轴突在目标嗅神经束中识别的“地址”的各个方面，并确定这些轴突和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；以及(2)确定一氧化氮在触角叶中性同构和性二形小球的发育中所起的作用。一氧化氮是一种气体细胞间信号分子，似乎是通过发育嗅轴突释放出来的。该项目利用蛾子嗅觉系统的相对细胞简单性，除了电生理、生化和分子生物学方法外，还使用最先进的显微镜方法，有望为开发更难获得的哺乳动物嗅觉系统提供见解。

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.