Neural Mechanisms of Olfactory Pattern Recognition

摘要 嗅觉系统对气味进行编码和分析。化学物质与受体大家族成员结合 根据不同的化学特征调整的蛋白质。虽然我们有一个全面的受体基因清单 作为嗅觉检测的基础，我们还远远没有对 嗅觉系统检测到的化学特征。 这项提议利用了四个发展--记录整个嗅觉的输出的能力 气味系统(犁鼻系统)，一大类结构坚硬的气味物质(硫酸盐、羧化和 糖醛酸化类固醇)，一种识别具有特定配体检测的受体基因的新工具(S) Profile，以及异位表达所选受体基因并研究其功能的新工具-TO 建立第一个系统范围内对嗅觉系统如何表示化学世界的理解。这个 首要目标是开发类似于锥体角色的洞察力(并具有类似的预测能力) 光感受器调谐曲线在我们对颜色视觉的理解中。 该提案的具体目的是(1)揭示受体序列和 通过去孤构化一个大的犁鼻受体基因亚家族的气味结构；(2)揭示新的 组合编码原理通过对犁鼻系统覆盖范围的全系统分析， 通过大的配体筛选和结构特征的定量分析来实现冗余性和特异性 激活每个感受器所需的；以及(3)识别感官体验形成的机制 感觉神经元调谐。初步数据表明，类固醇代谢物的结构刚性对 在很大程度上提高了这些目标的可控性，支持在全系统范围内进行定量和预测性分析。

ABSTRACT The olfactory system encodes and analyzes odorants. Chemicals bind to members of large families of receptor proteins tuned to different chemical features. While we have a comprehensive inventory of the receptor genes that underlie olfactory detection, we are far from having a similarly comprehensive understanding of the chemical features detected by olfactory systems. This proposal leverages four developments—the ability to record the output of an entire olfactory system (the vomeronasal system), a large and structurally-rigid class of odorants (sulfated, carboxylated, and glucuronidated steroids), a new tool to identify the receptor gene(s) that have particular ligand detection profiles, and a new tool for ectopically expressing a chosen receptor gene and studying its function—to develop the first system-wide understanding of how an olfactory system represents the chemical world. The overarching goal is to develop insights analogous to (and with similar predictive power to) the role of cone photoreceptor tuning curves in our understanding of color vision. The specific aims of the proposal are (1) to reveal relationships between receptor sequence and odorant structure by deorphanizing a large subfamily of vomeronasal receptor genes; (2) to reveal new principles of combinatorial coding through a system-wide analysis of the vomeronasal system's coverage, redundancy, and specificity via a large ligand screen and quantitative analysis of the structural features required for activating each receptor; and (3) to identify mechanisms by which sensory experience shapes sensory neuron tuning. Preliminary data suggest that structural rigidity of steroid metabolites contributes greatly to the tractability of these aims, supporting quantitative and predictive analysis on a system-wide scale.