Target-Defined Parallel Pathways in the Olfactory System

描述（由申请人提供）：感觉系统通过多个并行路径处理传入信息，这些路径将外部环境的复杂表征分解为不同的处理流。这些平行通路编码刺激特征的子集，并对统一的感官知觉的特定方面做出贡献——例如，视觉中的运动和形式。虽然被很好地描述并被认为是其他方式（如视觉）感觉处理的基础，但嗅觉系统中的平行通路仍然知之甚少。该项目将首次描述嗅球（嗅觉系统中处理的第一个突触水平）的输出如何在其投射目标的气味信息表征方面有所不同。该项目使用最新开发的光学、遗传和分子工具来记录单个嗅球输出神经元的活动，这些神经元根据其轴突投射到初级嗅皮层的特定区域进行标记。为了实现这一目标，基因编码的Ca2+报告蛋白（GCaMP）或光激活通道（ChR2）将在嗅球投射神经元中表达，使用病毒载体驱动cre -重组酶依赖的转基因表达和在嗅球二尖瓣细胞和簇状细胞中选择性表达cre -重组酶的小鼠系。实验利用了我们实验室新发现的事实，即这些神经元可以通过轴突感染，只允许那些投射到嗅皮层特定区域的神经元表达。然后，在麻醉和清醒的小鼠中，通过体内成像或电生理记录这些目标神经元的气味反应。该方法的所有方面最近都在我们的实验室中得到了发展并得到了有力的应用。利用这种方法，我们将探讨投射到不同嗅觉皮质区域的神经元，它们的气味诱发反应特性和它们在清醒行为动物中的调节程度是如何不同的。这些实验将解决有关嗅球产生的嗅觉处理流的本质的重要问题：对不同皮层目标的投射是否携带不同的感觉信息表征-例如，在视觉系统中运动和形式的平行表征中发生a ？如果是这样，在气味编码和气味感知的背景下，这些差异的本质是什么？此外，不同种类的嗅球输出神经元——通常通过它们的树突形态和体细胞位置来识别——是否根据它们的皮层目标映射到不同的解剖路径，或者根据它们的气味反应特性映射到不同的功能编码流？总之，提出的实验应该导致在功能和行为背景下理解平行嗅觉处理流的重大进展。

DESCRIPTION (provided by applicant): Sensory systems process incoming information via multiple, parallel pathways that break the complex representation of the external environment into distinct processing streams. These parallel pathways encode a subset of stimulus features and contribute to specific aspects of a unified sensory percept - for example, motion and form in vision. While well-described and recognized as fundamental to sensory processing in other modalities such as vision, parallel pathways in the olfactory system remain poorly understood. This project will characterize for the first time how outputs from the olfactory bulb - the first synaptic level of processing in the olfactory system - differ in their representation of odor information as a function of their projection target. The project uses recently-developed optical, genetic and molecular tools to enable recording activity from individual olfactory bulb output neurons tagged according to their axonal projection to specific regions of primary olfactory cortex. To accomplish this, genetically-encoded Ca2+ reporter proteins (GCaMP) or light-activated channels (ChR2) will be expressed in olfactory bulb projection neurons using a viral vector driving Cre-recombinase dependent expression of the transgene and a mouse line expressing Cre-recombinase selectively in mitral and tufted cells of the olfactory bulb. The experiments take advantage of the fact - newly established by our laboratory - that these neurons can be infected through their axons, allowing expression in only those neurons projecting to specific areas of olfactory cortex. Odor responses in such target-defined neurons will then be recorded with in vivo imaging or with electrophysiology in both anesthetized and awake mice. All aspects of this methodology have recently been developed and work robustly in our laboratory. Using this approach we will ask how neurons projecting to distinct olfactory cortical areas differ with respect to their odorant- evoked response properties and their degree of modulation in the awake, behaving animal. The experiments will address important questions regarding the nature of olfactory processing streams that emerge from the olfactory bulb: Do projections to different cortical targets carry distinct representations of sensory information - a occurs, for example, in the parallel representations of motion and form in the visual system? If so, what is the nature of these differences in the context of odor coding and odor perception? In addition, do the different classes of olfactory bulb output neurons - classically identified by ther dendritic morphology and somatic location - map to distinct anatomical pathways according to their cortical targets or to distinct functional coding streams according to their odor response properties? Together the proposed experiments should lead to a significant advance in understanding parallel olfactory processing streams in a functional and behavioral context.