CA2+/CAMP SIGNALING IN DEVELOPMENT OF FOREBRAIN CIRCUITS

前脑回路发育中的 CA2 /CAMP 信号传导

• 批准号: 6391638
• 负责人: TONY AI PHAM
• 金额: $ 14.96万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-09-01 至 2005-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6391638
• 关键词: biological signal transduction; cAMP response element binding protein; calcium flux; cyclic AMP; developmental neurobiology; gene expression; genetic regulation; genetically modified animals; laboratory mouse; neocortex; neural plasticity; neurogenesis; prosencephalon; synaptogenesis; thalamus

DESCRIPTION: The precise synaptic connectivity of neurons in the mammalian brain is the underlying cellular substrate that governs perception and behavior. The major psychiatric illnesses, such as schizophrenia and depression, may be caused by abnormalities in the connectivity of forebrain neurons. However, the molecular mechanisms that instruct the precise development of forebrain connectivity are largely unknown. This application examines the hypothesis that cellular processes mediated by calcium and cyclic AMP are critical for the refinement and maturation of neural circuits in the thalamus and neocortex, key forebrain structures that mediate conscious perception. Using the visual system as the experimental model, the specific aims of the research are: (1) to examine the mechanisms that drive calcium/cAMP-regulated gene expression during the development of neocortical and thalamic circuitry, (2) to examine the processes that lead to the down-regulation of neocortical calcium/cAMP-regulated gene expression with maturation, (3) to determine the impact of disruption of calcium/cAMP signaling on neocortical plasticity and thalamic connectivity, (4) to construct a transgenic mouse line that has a thalamus specific disruption of the calcium/cAMP-regulated transcription factor CREB. These experiments will help elucidate how calcium/cAMP signals translate sensory experience into patterns of gene expression, and determine the impact of disruption of calcium/cAMP signaling on neural connectivity. The investigator is a psychiatrist whose long-term interest is to understand how neuronal connectivity develops early in life and how it is modified by experience, with the hope that this knowledge will provide insight into the cellular and molecular abnormalities that underlie behavioral and perceptual disorders. He will have an appointment as assistant professor at the University of Washington School of Medicine. His transition towards research independence will be undertaken with mentoring from Dr. Daniel Storm and Dr. Mark Hamlin of the University of Washington. Also, several collaborations are planned, namely with Dr. Alcino Silva (UCLA), Dr. Barbara Gordon-Lickey (University of Oregon), and Dr. John Neumaier (University of Washington), that will result in a significant broadening of research experience.

描述：哺乳动物神经元的精确突触连接 大脑是控制感知的基本细胞基质， 行为主要的精神疾病，如精神分裂症和 抑郁症，可能是由前脑连接异常引起的， 神经元然而，指导精确的生物学行为的分子机制 前脑连接的发展在很大程度上是未知的。本申请 检查的假设，细胞过程介导的钙和循环 AMP对于脑中神经回路的完善和成熟至关重要。 丘脑和新皮质，是调节意识的关键前脑结构 perception.以视觉系统为实验模型， 研究的目的是：（1）研究驱动机制， 钙/cAMP调控的基因表达在新皮质发育过程中的作用 和丘脑电路，（2）检查导致 下调新皮质钙/cAMP调节的基因表达， 成熟，（3）以确定钙/cAMP信号传导中断的影响 对新皮层可塑性和丘脑连通性的影响，（4）构建一个 转基因小鼠系，其具有丘脑特异性的 钙/cAMP调节的转录因子CREB。这些实验将有助于 阐明钙/cAMP信号如何将感觉经验转化为模式 的基因表达，并确定钙/cAMP的破坏的影响， 神经连接的信号 研究者是一名精神科医生，其长期兴趣是了解 神经元连接如何在生命早期发展，以及它如何被 经验，希望这些知识将提供洞察力， 细胞和分子异常是行为和知觉的基础 紊乱他将被任命为这所大学的助理教授 来自华盛顿医学院。他向研究独立的过渡 将在丹尼尔斯托姆博士和马克哈姆林博士的指导下进行。 华盛顿大学。此外，还计划开展几项合作，即 Alcino Silva博士（加州大学洛杉矶分校），Barbara Gordon-Lickey博士（俄勒冈州大学）， 和约翰·诺伊迈尔博士（华盛顿大学），这将导致一个 大大拓宽了研究经验。