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）：通过多个平行的路径将感官系统处理输入信息，这些路径将外部环境的复杂表示形式分为不同的处理流。这些平行路径编码刺激特征的子集，并有助于统一感觉感知的特定方面 - 例如，在视觉中的运动和形式。虽然描述良好，并且被认为是视觉等其他方式中感觉处理的基础，但嗅觉系统中的平行途径仍然很少理解。该项目将首次表征嗅球的输出如何（嗅觉系统中的第一个突触级别处理水平）在其异味信息的表示方面有所不同，这是其投影目标的函数。该项目使用最近开发的光学，遗传和分子工具，从而从单个嗅球输出神经元根据其轴突投影对原发性嗅觉皮质的特定区域标记的单个嗅球输出神经元进行记录活性。为此，使用病毒载体驱动CRE-结构酶依赖于跨性别的Cre-recombinase依赖性表达CRE-RECIBINASE选择性地表达Cre-Recibinase酶选择性地在MIRB和Tufterd的细胞中，使用病毒载体依赖Cre-cobinase依赖CRE-成分酶表达，将在嗅球投影神经元中表达遗传编码的Ca2+报道蛋白（GCAMP）或光活化通道（CHR2）（CHR2）。实验利用了我们实验室新确定的事实，即这些神经元可以通过轴突感染，从而只能在那些投射到嗅觉皮质特定区域的神经元中表达。然后，在麻醉和清醒小鼠中，将使用体内成像或电生理学记录这种目标定义的神经元中的气味反应。最近已经开发了这种方法的所有方面，并在我们的实验室中努力工作。使用这种方法，我们将询问神经元投射到不同嗅觉皮质区域的神经元在其气味诱发的反应特性及其在醒着中的调节程度方面有所不同。这些实验将解决有关从嗅球出现的嗅觉加工流的性质的重要问题：对不同皮层目标的投影是否具有感官信息的不同表示 - 例如，在视觉系统中的运动和形式的平行表示中发生了A？如果是这样，在气味编码和气味感知的背景下，这些差异的性质是什么？此外，不同类别的嗅球输出神经元 - 通过树突形态和躯体位置在经典上鉴定 - 根据其皮质靶标或根据其气味响应特性，将其映射到不同的解剖途径或根据其异味响应特性而定为不同的功能编码流？提出的实验共同使在功能和行为环境中的平行嗅觉处理流方面有重大进步。