Target-Defined Parallel Pathways in the Olfactory System

嗅觉系统中目标定义的平行通路

• 批准号: 8793786
• 负责人: DALE M WACHOWIAK
• 金额: $ 31.35万
• 依托单位: UNIVERSITY OF UTAH
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-02-10 至 2016-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8793786
• 关键词: Address; Anesthesia procedures; Animals; Area; Attention; Automobile Driving; Axon; Behavior; Behavioral; Brain; Breathing; Calcium; Cells; Code; Complex; Detection; Disease; Electrophysiology (science); Environment; Genetic; Head; Health; Image; Individual; Injury; Laboratories; Lead; Light; Link; Location; Maps; Methodology; Modality; Molecular Genetics; Morphology; Motion; Mus; Nature; Nervous system structure; Neurons; Odors; Olfactory Cortex; Olfactory Pathways; Optics; Output; Pathway interactions; Pattern; Perception; Problem Solving; Process; Property; Proteins; Relative (related person); Reporter; Reporter Genes; Response to stimulus physiology; Sensory; Sensory Process; Shapes; Smell Perception; Specificity; Stimulus; Stream; Structure; Synapses; Testing; Therapeutic; Time; Viral Vector; Virus Diseases; Vision; Visual system structure; Wakefulness; Whole-Cell Recordings; Work; awake; extracellular; imaging modality; in vivo; in vivo imaging; information processing; innovation; insight; neuroregulation; novel; olfactory bulb; optogenetics; parallel processing; recombinase; relating to nervous system; research study; response; selective expression; sensory system; targeted imaging; tool; transgene expression; two-photon

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.

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示分解为不同的处理流。这些并行路径编码刺激特征的子集，并有助于统一感官知觉的特定方面 - 例如，视觉中的运动和形式。尽管嗅觉系统中的平行通路已被充分描述并被认为是视觉等其他方式中感觉处理的基础，但人们对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级别）的输出在气味信息表示上如何根据其投影目标而有所不同。该项目使用最近开发的光学、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，将使用驱动 Cre 重组酶依赖性转基因表达的病毒载体和表达 Cre 重组酶的小鼠系，在嗅球投射神经元中表达基因编码的 Ca2+ 报告蛋白 (GCaMP) 或光激活通道 (ChR2)选择性地存在于嗅球的二尖瓣和簇状细胞中。这些实验利用了我们实验室新建立的事实，即这些神经元可以通过其轴突感染，从而仅在那些投射到嗅觉皮层特定区域的神经元中表达。然后，通过体内成像或电生理学记录麻醉和清醒小鼠中此类目标定义神经元的气味反应。该方法的各个方面最近都已在我们的实验室中得到开发并运行良好。使用这种方法，我们将询问投射到不同嗅觉皮层区域的神经元在其气味诱发的反应特性及其在清醒、行为动物中的调节程度方面有何不同。这些实验将解决有关从嗅球产生的嗅觉处理流的性质的重要问题：对不同皮层目标的投射是否携带不同的感觉信息表示——例如，在视觉中运动和形式的并行表示中会发生这种情况系统？如果是这样，在气味编码和气味感知方面这些差异的本质是什么？此外，不同类别的嗅球输出神经元（通常通过树突形态和体细胞位置来识别）是否根据其皮质目标映射到不同的解剖路径，或根据其气味反应特性映射到不同的功能编码流？总之，所提出的实验应该会在功能和行为背景下理解并行嗅觉处理流方面取得重大进展。