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Piriform cortex: sequential developmental events

梨状皮层：顺序发育事件

基本信息

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
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/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

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.

项目摘要-摘要