Piriform cortex: sequential developmental events

梨状皮层：顺序发育事件

• 批准号: 10442245
• 负责人: Charles A Greer
• 金额: $ 41.88万
• 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 2027-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10442245
• 关键词: Address; Adult; Afferent Neurons; Anterior; Architecture; Attention; Axon; Brain; Cells; Cilia; Clustered Regularly Interspaced Short Palindromic Repeats; Code; Complex; Contralateral; Data; Development; Didelphidae; Electroporation; Epithelial; Event; FOXP2 gene; Foundations; Ganglia; Genetic; Goals; Interneurons; Ipsilateral; Knock-out; Knowledge; Lateral; Lens development; Ligand Binding; Maps; Methods; Molecular; Molecular Genetics; Mus; Neocortex; Neuroglia; Neurons; Odorant Receptors; Odors; Olfactory Epithelium; Olfactory Pathways; Olfactory tract; Play; Property; Radial; Rattus; Recurrence; Resolution; Role; SOX5 gene; Seminal; Smell Perception; Specificity; Structure; Study models; Surface; Synapses; Testing; TimeLine; Work; anterior commissure; association cortex; connectome; course development; exhaustion; hippocampal pyramidal neuron; in utero; innovation; insight; migration; neocortical; nerve supply; neural circuit; neuroblast; neurogenesis; novel; olfactory bulb; olfactory bulb glomeruli; olfactory sensory neurons; piriform cortex; receptor; segregation; sensory system; spatiotemporal; tool; transcription factor

Project Summary – Abstract 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/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 do synapses first appear in mouse PCX and when do they achieve laminar segregation? What is the organization of the ipsi- and contralateral association axons that likely contribute to the cortical coding of odors in ensembles of neurons? 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 addresses the emergence of synaptic circuits in PCX and tests the hypothesis that it occurs in a spatio-temporal format that distinguishes the laminar specificity of circuits. Aim 2 addresses the PCX associational connectome, both ipsilateral and contralateral via the anterior commissure. Aim 3 tests the spatiotemporal expression of transcription factors (TFs) that we hypothesize are important in establishing PCX pyramidal neuron identity and contributions to the association axon network in PCX. Selective TFs will be knocked out using CRISPR to determine their role at a more granular level. Collectively these innovative studies will provide new insight into the mechanisms regulating the organization of PCX and the foundations of odor coding in PCX.

项目摘要-摘要 当气味配体与分子结合时，气味的感觉开始于嗅觉上皮 嗅觉感觉神经元纤毛上表达受体，每种受体仅表达~1200中的1种 候选受体。当感觉神经元轴突离开上皮时，它们在 嗅球和所有轴突都来自表达相同气味感受器的神经元 仅汇聚成2/3的肾小球/嗅球。然而，汇聚和分立的电路 梨状皮质(PCX)内嗅球不明显，至少大体不明显。梨状肌的传入投射 表现出分歧和广泛的分布。此外，与更广泛研究的新大脑皮层相比， 3层梨状古大脑皮层没有显示出明确的柱状结构，留下了一个悬而未决的问题 从新皮质学到的原理是否可以应用于理解梨状叶。我们所做的大部分 梨状肌的神经元和突触组织的知识来自于对大鼠和负鼠的早期研究， 这一点虽然重要，但并没有从当代的遗传和分子工具中受益。鼠标，它 已经成为研究嗅觉上皮和嗅球的主要哺乳动物模型 从这些新工具中获得了不可估量的好处。然而，很少有应用于 当代遗传学和分子方法在小鼠梨状皮质研究中的应用。我们悲哀地留在这里 对小鼠梨状皮质最基本的特征一无所知突触何时首次出现在 小鼠PCX和它们什么时候实现层状分离？国际和平研究所的组织是什么--以及 对侧联合轴突可能对气味的皮质编码有贡献 神经元？其命运和特异性背后的分子机制/转录因子是什么 PCX神经元/结构？为了开始解决我们知识中的这些重大差距，我们提议3 具体目标：目标1解决了PCX中突触回路的出现，并检验了以下假设 它以时空的形式出现，区分了电路的层流特性。AIM 2的地址 经前连合的同侧和对侧的PCX联合药隔。目标3 测试转录因子(TF)的时空表达，我们假设转录因子在 建立PCX锥体神经元的身份和对PCX内联合轴突网络的贡献。 选择性的TF将使用CRISPR被淘汰，以在更细粒度的水平上确定它们的角色。 总而言之，这些创新的研究将为调节 PCX的组织和PCX中气味编码的基础。