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Novel Developmental Pathways Underlying Psychiatric Disorders

精神疾病背后的新发育途径

基本信息

批准号：
9341394
负责人：
Anju Vasudevan
金额：
$ 41.63万
依托单位：
MCLEAN HOSPITAL
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：
2016-09-01 至 2021-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9341394
关键词：
Adopted Adult Affect Autistic Disorder Autocrine Communication Axon Behavior Blood Vessels Blood flow Brain Cell Proliferation Cells Cerebral cortex Complex Cues Darkness Development Disease Embryo Embryonic Development Endothelial Cells Event Feedback GABA Receptor Genes Glutamates Impairment In Vitro Interneurons LOX gene Light Link Mediating Mental Health Mental disorders Molecular Morphology Nature Neuroglia Neurons Neurophysiology - biologic function Pathway interactions Pattern Pattern Formation Population Positioning Attribute Process Prosencephalon Public Health Radial Receptor Signaling Reporting Research Route Schizophrenia Signal Pathway Signal Transduction Technology Telencephalon Testing Vascular System Ventricular Work angiogenesis design gamma-Aminobutyric Acid in vivo information processing insight knockout gene migration nerve stem cell neurogenesis neurovascular novel postnatal prenatal receptor

项目摘要

Abstract The cerebral cortex is essential for integration and processing of information that is required for most behaviors. Correct functioning of the cerebral cortex necessitates the concerted assembly of circuits involving glutamatergic projection neurons and GABAergic interneurons. The exquisitely precise laminar arrangement of neurons, axon collaterals and dendritic processes arises during embryonic development when neurons migrate successively from proliferative ventricular zones to coalesce into specific cortical layers. While radial glia was identified as substrates or guide rails for migration of projection neuron precursors to the cortical plate in the early seventies, the substrate for GABAergic interneuron migration was a missing link. Our recent work has shown that pre-formed vascular networks in the embryonic forebrain are strategically positioned to fulfill the formidable task of providing support and guidance cues to GABA neurons as they migrate from the subpallium to the developing cerebral cortex. This application will examine this novel paradigm of endothelial cell-neuron interactions at detailed cellular and molecular levels. It will elucidate the importance of new signaling mechanisms via forebrain endothelial cells that were hitherto believed to be exclusively neuronal. It will examine how alterations in these novel developmental pathways disturb hierarchical vascular patterns; perturb neuronal migration and cortical organization. Results will illustrate a powerful impact on cerebral cortex circuitry, blood flow and postnatal behavior with new significance for psychiatric disorders.

摘要