Piriform cortex: sequential developmental events

梨状皮层：顺序发育事件

• 批准号: 9171950
• 负责人: Charles A Greer
• 金额: $ 35.38万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-12-01 至 2019-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9171950
• 关键词: Address; Adult; Affect; Afferent Neurons; Architecture; Axon; Bone structure; Brain; Cell division; Cells; Cilia; Code; Data; Deafferentation procedure; Development; Didelphidae; Dimensions; Electroporation; Epithelium; Event; Foundations; Genetic; Goals; Interneurons; Knowledge; Life; Ligand Binding; Link; Logic; Methods; Molecular; Molecular Analysis; Molecular Probes; Mus; Neocortex; Nervous system structure; Neurons; Ocular dominance columns; Odorant Receptors; Odors; Olfactory Cortex; Olfactory Epithelium; Olfactory Pathways; Olfactory tract; Pattern; Perinatal; Preparation; Procedures; Property; Rattus; Reporting; Role; Seminal; Sensory; Sensory Process; Shapes; Site; Smell Perception; Specificity; Structure; Study models; Surface; Synapses; Testing; Time; TimeLine; Visual system structure; Work; course development; experience; genetic manipulation; hippocampal pyramidal neuron; in utero; insight; lens; mitral cell; mouse development; neocortical; neural circuit; neurogenesis; neuron apoptosis; neuronal circuitry; olfactory bulb; olfactory bulb glomeruli; olfactory sensory neurons; piriform cortex; postnatal; public health relevance; receptor; segregation; sensory input; sensory system; spatiotemporal; tool; transcription factor

DESCRIPTION (provided by applicant): The perception of odors begins in the olfactory epithelium when odorant ligands bind to molecular receptors expressed on the cilia of the olfactory sensory neurons, each of which expresses only 1 of 1200 candidate receptors. As the sensory neuron axons exit the epithelium they progress over the surface of the olfactory bulb and all of the axons coming from neurons expressing the same odorant receptor converge into only 2-3 glomeruli in the olfactory bulb. However, the convergence and discrete circuitry of the olfactory bulb is not apparent in piriform cortex (PCX), at least grossly. Afferent projections to piriform appear divergent and broadly distributed. Moreover, in contrast to the more widely studied neocortex, the 3 layer piriform paleocortex does not exhibit a definitive columnar structure, leaving open the question of whether principles learned from neocortex can be applied to understanding piriform. Most of what we know of the neuronal and synaptic organization of piriform has come from early studies of rat and opossum that while important did not benefit from contemporary genetic and molecular tools. The mouse, which has emerged as the dominant mammalian model for studies of the olfactory epithelium and bulb, has benefited immeasurably from these new tools. However, there are few examples of the application of contemporary genetic and molecular methods to studies of mouse piriform cortex. We remain woefully ignorant of the most fundamental features of mouse piriform cortex: When are the PCX neurons born and what is the timeline for the laminar organization? When do synapses first appear in mouse PCX and when do they achieve laminar segregation? What is the role of functional activity in the dynamics of PCX development and final organization? What are the molecular mechanisms/transcription factors underlying the fate and specificity of PCX neurons/structure? To begin addressing these significant gaps in our knowledge we are proposing 3 specific aims: Aim 1 - Test the hypothesis that the subpopulations of neurons in PCX have distinct developmental lineages and that the emergence of laminar specificity occurs along a coordinated timeline; Aim 2 - Test the hypothesis that odor experience, afferent activity, influences PCX neuron fate and synaptic circuitry; and Aim 3 - Test the hypothesis that candidate transcription factor expression occurs in a sequentially defined manner and is an essential determinant of PCX neuronal fate.

描述（由申请人提供）：当气味配体与嗅觉感觉神经元纤毛上表达的分子受体结合时，气味的感知开始于嗅觉上皮，每个嗅觉神经元纤毛仅表达 1200 种候选受体中的一种。当感觉神经元轴突离开上皮时，它们在嗅球表面上前进，并且来自表达相同气味受体的神经元的所有轴突仅汇聚到嗅球中的 2-3 个肾小球中。然而，嗅球的会聚和离散电路在梨状皮层（PCX）中并不明显，至少在总体上是这样。梨状体的传入投射显得分散且分布广泛。此外，与更广泛研究的新皮质相比，3层梨状古皮质并未表现出明确的柱状结构，从而留下了从新皮质学到的原理是否可以应用于理解梨状的问题。我们对梨状神经元和突触组织的了解大部分来自对大鼠和负鼠的早期研究，这些研究虽然很重要，但并没有受益于当代的遗传和分子工具。小鼠已成为研究嗅觉上皮和嗅球的主要哺乳动物模型，它从这些新工具中受益匪浅。然而，应用当代遗传和分子方法研究小鼠梨状皮层的例子很少。遗憾的是，我们仍然对小鼠梨状皮层最基本的特征一无所知：PCX 神经元何时诞生以及层状组织的时间表是什么？突触何时首次出现在小鼠 PCX 中以及它们何时实现层状分离？功能活动在 PCX 开发和最终组织的动态中扮演什么角色？ PCX 神经元/结构的命运和特异性背后的分子机制/转录因子是什么？为了开始解决我们知识中的这些重大差距，我们提出了 3 个具体目标： 目标 1 - 检验 PCX 中的神经元亚群具有不同的发育谱系以及层状特异性的出现沿着协调的时间线发生的假设；目标 2 - 测试气味体验、传入活动影响 PCX 神经元命运和突触回路的假设；目标 3 - 检验以下假设：候选转录因子表达以顺序定义的方式发生，并且是 PCX 神经元命运的重要决定因素。