Ontogeny of Central Neural Taste Responses

项目摘要/摘要 发展中的味觉系统具有令人印象深刻的结构和功能变化。中环 啮齿动物的味觉通路在正常发育过程中尤其可塑性，甚至在第一次突触传递时也是如此。 从结构上讲，将味觉信息从味蕾传递到 延髓中的孤束核(NST)的大小被缩小，或被“修剪”到大约其大小的一半-- 从断奶前开始，持续到断奶后10天左右。从功能上讲， “修剪”的发生与味觉神经中味觉诱发神经活动的增加是一致的，这表明 必要的依赖于活动的组件。此外，神经活动的实验操作和 动物在发育过程中的饮食历史中断了终端田地的正常“修剪”，这表明 活动依赖因子和活动非依赖因子都在回路的发育过程中发挥作用。 精致。这个项目的长期目标是了解中央味觉系统是如何组装的 然后通过经验来提炼。这项提议的具体目的是研究1)神经元是如何 舌头前2/3处的单个味蕾映射到NST，以及在 正常发育和成年小鼠在整个发育过程中改变了神经活动或改变了 饮食历史，以及2)神经免疫分子级联反应在正常发育过程中是如何运作的 在改变神经活动或改变饮食历史的小鼠身上中断。该项目的目标将是 通过单一味蕾标记、外周味觉神经记录、中枢 神经系统束追踪，突触成分的光镜和电子显微镜广泛分析 水平，以及光遗传恢复功能的实验。这些研究将提供新的和重要的 关于中枢味觉系统的发育和可塑性的信息，以及 在发育过程中的免疫和味觉系统，更广泛地说，它们将在确定 母体饮食和味觉活动在组织味觉发育中的作用。

Project Summary/Abstract The developing gustatory system is characterized by impressive structural and functional changes. The central taste pathway in rodents is especially plastic during normal development, even at the first synaptic relay. Structurally, the terminations (i.e., terminal fields) of neurons carrying taste information from taste buds to the nucleus of the solitary tract (NST) in the medulla are reduced in size, or “pruned”, to about half of their size -- beginning just before weaning and extending for about 10 days after weaning. Functionally, the period of “pruning” occurs coincident with the increase in taste-elicited neural activity in gustatory nerves, suggesting a requisite activity-dependent component. Moreover, experimental manipulations of neural activity and the animal’s dietary history during development interrupts the normal “pruning” of terminal fields, indicating that both activity-dependent and activity-independent factors play a role in the developmental process of circuit refinement. The long-term goal of this project is to understand how the central gustatory system is assembled and then refined by experience. The specific aims of this proposal examine 1) how neurons that innervate single taste buds on the anterior 2/3 of the tongue map onto the NST and how the projections change during normal development and in adult mice that have altered neural activity throughout development or an altered dietary history, and 2) how the neuro-immune molecular cascade operating during normal development is interrupted in mice that have altered neural activity or an altered dietary history. The aims of the project will be addressed through coordinated techniques of single taste bud labels, peripheral taste nerve recordings, central nervous system tract tracing, extensive analyses of synaptic elements at the light and electron microscopic level, and optogenetic recovery of function experiments. These studies will provide new and important information about the development and plasticity of the central gustatory system, the interplay between the immune and gustatory systems during development, and more broadly, they will be useful in determining the role that the maternal diet and taste-elicited activity have on organizing the developing sense of taste.