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）：大脑皮层是高级大脑功能的所在地，负责感觉知觉、认知过程、随意运动和意识。人类大脑皮层的异常会导致神经和精神疾病，例如癫痫、精神分裂症和自闭症。人类大脑皮层功能解剖学的一个关键特征是其沿切向维度组织成功能不同的区域。在大脑发育过程中，高度异质的细胞类型必须在这些区域内部和之间精确地组装成独特的神经回路，以控制复杂的行为和认知过程。编码皮质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。该提案详细介绍了在耶鲁大学神经生物学教授 Nenad Sestan 博士指导下的博士后研究和专业发展的 3 年计划。该研究员将研究形成皮质内投射神经元异质性和投射同一性的分子基础的机制。该研究员将利用他在神经发育生物学方面现有的专业知识，显微镜、组织学和细胞生物学。他将进一步发展大脑皮层发育的结构和功能、神经回路追踪、转录分析、单细胞分选和先进的小鼠遗传技术，通过追求以下具体目标：1.) 听觉皮层关联区域 (A2) 的皮质内投射的表征，2.) 皮质内投射神经元亚型的转录分析和表征A2 和 3.) 破译 A2 中建立皮质内投射神经元异质性的分子机制。 Sestan 博士在皮质发育和基因组学、小鼠遗传学以及远程投射电路研究方面的专业知识将为确保成功完成这些目标提供必要的科学指导和技术能力。研究员和资助者还制定了详细的专业技能发展计划。这里提出的研究和培训计划，以及该研究员选择的导师，将为该研究员的学术生涯目标提供良好的培训，研究大脑皮层的发育神经生物学及其疾病功能障碍。