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: 8479072
• 负责人: DALE M WACHOWIAK
• 金额: $ 31.71万
• 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 2018-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8479072
• 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; 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; System; Testing; Therapeutic; Time; Viral Vector; Virus Diseases; Vision; Visual system structure; Wakefulness; Whole-Cell Recordings; Work; awake; extracellular; imaging modality; in vivo; information processing; innovation; insight; novel; olfactory bulb; optogenetics; parallel processing; public health relevance; recombinase; relating to nervous system; research study; response; selective expression; sensory system; 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(申请人提供)：感官系统通过多个并行路径处理传入的信息，这些路径将外部环境的复杂表示分解为不同的处理流。这些平行通路编码刺激特征的子集，并对统一感觉的特定方面做出贡献--例如，视觉中的运动和形式。虽然在视觉等其他形式的感觉加工中被很好地描述和认识为基础，但嗅觉系统中的平行通路仍然知之甚少。这个项目将首次描述嗅球的输出--嗅觉系统中的第一个突触处理水平--在气味信息的表示上是如何随着投射目标的不同而不同的。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，这些神经元根据轴突投射到初级嗅觉皮质的特定区域进行标记。为了实现这一点，利用驱动依赖于Cre重组酶的转基因基因表达的病毒载体和选择性表达Cre重组酶的小鼠细胞系，将遗传编码的钙报告蛋白(GCaMP)或光激活通道(ChR2)表达在嗅球投射神经元中。这些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它们的轴突被感染，只允许在那些投射到嗅皮层特定区域的神经元中表达。然后，在麻醉和清醒的小鼠中，将用活体成像或电生理学记录这种靶标确定的神经元的气味反应。这一方法的所有方面都是最近开发出来的，并在我们的实验室有力地发挥了作用。使用这种方法，我们将询问投射到不同嗅觉皮质区域的神经元在它们的气味诱发反应特性和它们在清醒的行为动物中的调制程度方面有什么不同。这些实验将解决有关嗅球产生的嗅觉处理流的性质的重要问题：到不同皮质目标的投射是否携带感觉信息的不同表示-例如，在视觉系统中运动和形状的平行表示中发生？如果是，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，不同类别的嗅球输出神经元--通常由树突形态和躯体位置识别--是根据它们的皮质目标映射到不同的解剖路径，还是根据它们的气味反应特性映射到不同的功能编码流？总之，拟议的实验应该会在理解功能和行为背景下的并行嗅觉处理流方面取得重大进展。