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The Molecular Basis of Intracortical Projection Neuron Heterogeneity

皮质内投射神经元异质性的分子基础

基本信息

批准号：
9387639
负责人：
John C Silbereis
金额：
$ 0.08万
依托单位：
YALE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-09-30 至 2017-09-29
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9387639
关键词：
Alleles Anatomy Animal Model Area Auditory Auditory area Autistic Disorder Axon Behavior Biological Models Biology Brain Broca&apos s area Candidate Disease Gene Cell Separation Cells Cellular biology Cerebral cortex Cluster Analysis Clustered Regularly Interspaced Short Palindromic Repeats Communication Complex Conscious Data Set Development Developmental Biology Dimensions Disease Dyslexia Electroporation Ensure Epilepsy Evolution Fiber Functional disorder Genes Genetic Techniques Genetic Transcription Genetic study Genomics Goals Hemagglutinin Heterogeneity Histology Human Individual Injectable Label Location LoxP-flanked allele Maps Mental Processes Mental disorders Mentors Mentorship Microscopy Molecular Motor Motor Cortex Movement Mus Neurobiology Neurons Pathway interactions Perception Pilot Projects Population Principal Component Analysis RNA Reporter Research Research Training Ribosomal Proteins Ribosomes Role Schizophrenia Sensory Specific qualifier value Specificity Speech Speech Intelligibility Structure Synapses System Techniques Temporal Lobe Testing Training Transgenic Mice Universities Virus Work area striata base career cell type cognitive process developmental neurobiology differential expression experimental study frontal lobe genetic technology in utero in vivo knock-down language comprehension language processing nervous system disorder neural circuit professor public health relevance single cell sequencing skill acquisition speech processing transcriptome transcriptome sequencing

项目摘要

DESCRIPTION (provided by applicant): The cerebral cortex is the seat of higher brain function, responsible for sensory perception, cognitive processes, voluntary movement, and consciousness. Abnormalities of the human cerebral cortex cause neurological and psychiatric disorders, such as epilepsy, schizophrenia, and autism. A key feature of the functional anatomy of the human cerebral cortex is its organization into functionally distinct regions along its tangential dimension. During brain development, highly heterogeneous cell types must precisely assemble into unique neural circuits both within and between these areas to control complex behaviors and cognitive processes. The molecular mechanisms that encode cortical projection neuron subtype identity and synaptic specificity remain poorly understood. This proposal details a 3 year plan for postdoctoral research and professional development under the mentorship of Dr. Nenad Sestan, Professor of Neurobiology at Yale University. The fellow will investigate the mechanisms that form the molecular basis for intra-cortical projection neuron heterogeneity and projection identity. The fellow will build on his existing expertise in neurodevelopmental biology, microscopy, histology, and cell biology. He will further develop new expertise in the structure and function of the developing cerebral cortex, neural circuit tracing, transcriptional profiling, single-cell sorting, and advanced mouse genetic technologies by pursuing the following specific aims: 1.) Characterization of intra-cortical projections in association areas of auditory cortex (A2), 2.) Transcriptional profiling and characterization of intra-cortical projection neuron subtypes in A2, and 3.) Deciphering the molecular mechanisms that establish intra-cortical projection neuron heterogeneity in A2. The expertise of Dr. Sestan in cortical development and genomics, mouse genetics, and studies of long-range projection circuitry will provide the scientific guidance and technical capabilities necessary to ensure successful completion of these aims. The fellow and the sponsor have also developed a detailed plan for professional skills development. The research and training plan proposed here, along with the fellow's choice of mentor, will provide excellent training towards the fellow's goal of an academic career studying the developmental neurobiology of the cerebral cortex and its dysfunction in disease.

描述（由申请人提供）：大脑皮层是高级脑功能的所在地，负责感觉知觉、认知过程、自主运动和意识。人类大脑皮层的异常会导致神经和精神疾病，如癫痫、精神分裂症和自闭症。人类大脑皮层的功能解剖学的一个关键特征是其组织成沿其切向维度的功能不同的区域。在大脑发育过程中，高度异质的细胞类型必须精确地在这些区域内部和之间组装成独特的神经回路，以控制复杂的行为和认知过程。编码皮层投射神经元亚型身份和突触特异性的分子机制仍然知之甚少。本提案详细介绍了在耶鲁大学神经生物学教授Nenad Sestan博士指导下的3年博士后研究和专业发展计划。该研究员将研究形成皮层内投射神经元异质性和投射同一性的分子基础的机制。他将以他在神经发育生物学方面的现有专业知识为基础，