Piriform cortex: sequential developmental events

梨状皮层：顺序发育事件

基本信息

批准号：
10589155
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
项目类别：
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/10589155
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 Epithelium Event FOXP2 gene Foundations Genetic Goals Interneurons Ipsilateral Knock-out Knowledge Lateral Learning Lens development Ligand Binding Maps Methods Molecular Mus Neocortex Neuroglia Neurons Odorant Receptors Odors Olfactory Epithelium Olfactory Pathways Play Property Radial Rattus Recurrence Resolution Role SOX5 gene Seminal Shapes Smell Perception Specificity Structure Study models Surface Synapses Testing Work anterior commissure connectome course development hippocampal pyramidal neuron in utero innovation insight migration neocortical nerve supply neural circuit neuroblast neurogenesis novel olfactory bulb olfactory sensory neurons piriform cortex receptor segregation sensory system spatiotemporal timeline tool transcription factor

项目摘要

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.

项目总结 – 摘要当气味配体与分子结合时，气味的感知开始于嗅觉上皮嗅觉感觉神经元纤毛上表达的受体，每个受体仅表达约 1200 个中的 1 个当感觉神经元轴突离开上皮时，它们会在表面上前进。嗅球和所有轴突都来自表达相同气味受体的神经元仅汇聚成 2/3 肾小球/嗅球然而，汇聚和离散电路。嗅球在梨状皮层（PCX）中不明显，至少在梨状皮层的传入投射不明显。此外，与更广泛研究的新皮质相比，三层梨状古皮质没有表现出明确的柱状结构，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体的大部分内容。对梨状体的神经元和突触组织的了解来自对大鼠和负鼠的早期研究，那个重要的时期并没有受益于当代的遗传和分子工具。已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益匪浅，但应用的例子却很少。我们仍然悲哀地研究小鼠梨状皮层的现代遗传和分子方法。不知道小鼠梨状皮层最基本的特征突触什么时候第一次出现小鼠 PCX 以及它们何时实现层流分离？ ipsi- 和的组织是什么？对侧关联轴突可能有助于气味整体的皮质编码神经元的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，我们提出 3 具体目标：目标 1 解决 PCX 中突触回路的出现并测试以下假设：它以时空格式出现，区分目标 2 地址的层流特异性。 PCX 关联连接组，通过前连合同侧和对侧。测试我们所采取的转录因子（TF）的时空表达对于以下方面很重要建立 PCX 锥体神经身份以及对 PCX 中关联轴突网络的贡献。将使用 CRISPR 敲除选择性转录因子，以更精细地确定它们的作用。总的来说，这些创新研究将为调控机制提供新的见解。 PCX 的组织以及 PCX 中气味编码的基础。