Critical period in visual cortex: inhibitory circuits

视觉皮层的关键期：抑制回路

• 批准号: 6836512
• 负责人: SANDRA J KUHLMAN
• 金额: $ 4.99万
• 依托单位: COLD SPRING HARBOR LABORATORY
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-12-28 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6836512
• 关键词: Critical; period; visual; cortex; inhibitory

18. GOALS FOR FELLOWSHIP TRAINING AND CAREER INSTITUTION/COMPANY SUPERVISOPJEMPLOYER Gettysburg College Spring-Ford Dist. Pheonixville Dist. Northeastern University Dr Frederick C Davis Northeastern University Dr Frederick C Davis University of Kentucky Dr Douglas G McMahon I am fascinated by how sensory experiences form and refine the circuitry of the central nervous system that is used to code externally-driven neuronal activity. Intellectually, this training plan will enhance my ability to formulate testable hypotheses regarding the cellular mechanisms that drive the plasticity underlying behaviorally relevant sensory processing. Technically, I will receive training in 2-photon imaging and analysis useful for real-time imaging at high resolution in living tissue. I will receive training in mouse genetics using bacterial artificial chromosome technology to target specific cell types for physiological study and in vivo manipulation. These skills will enable me to succeed in my career goal of becoming an independent research scientist and train students of all levels in neurobiology. Future studies will examine the impact of light or other sensory stimulation on shaping on-going gene expression dynamics and neuronal activity in the context of developmental and behavioral states. The long-term goal is to more precisely define the cellular basis of how organisms adapt to their environment, and how to intervene when internal circuits are not well adapted. -li'll[-1"]i 19. NAME AND DEGREE(S) Z. Josh Huang 20. POSITION/RANK Assistant Professor 21. RESEARCH INTERESTS/AREAS experience-d _ependent p]astJcity neurotrophins mouse _enetics 22.DES RcIPeTIOntrI.DsosnuotmexnceedusraoceGpreov,nids%cde)understhaonwdexperiesnhcaepbersaifnunctioRn.ecesnttudiiensvisual cortex suggest that the maturation of intracortical inhibitory circuits is necessary to initiate and drive ocular dominance plasticity during the critical period. However, the maturation and regulation of the specific type of inhibitory circuit involved is not understood. Critical period plasticity is also modulated by visual deprivation and BDNF over-expression, although the cellular mechanisms remain unknown. Here we hypothesize that the functional maturation of a specific subtype of GABAergic neurons, parvalbumin (Pv) basket interneurons, are a component of the inhibitory mechanism underlying critical period platicity, and a cellular target of experience deprivation and BDNF regulation. Using bacterial artificial chromosome transgenic (BAC) mice expressing GFP in Pv-interneurons, we will characterize the morphological and physiological development of Pv-interneurons using two photon laser scanning microscopy and electrophysiology in brain slices. We will then examine the effects of dark rearing on the maturation of Pv-interneurons. Finally, we will test the role of BDNF in experience-dependent maturation of Pv-interneurons by blocking trkB signaling using BAC transgenic mice expressing a dominant negative form of trkB receptor specifically in Pv-interneurons. These results will reveal a mechanism by which experience shapes function of an identified inhibitory network and provide strong evidence that maturation of the Pv-interneuron circuit facilitates the coding of visual information necessary to drive ocular dominance plasticity. The knowledge gained will aid in the design of drug treatments in diseased states such as epilepsy and schizophrenia. PHS 416-1 (Rev. 12/98) Form Page 2 BB cc Table of Contents ========================================Section End===========================================

18.研究金培训和职业机构/公司SuPERVISOPJEMPLOYER Gettysburg College Spring-Ford Dist的目标。菲奥尼克斯维尔区。东北大学弗雷德里克·C·戴维斯博士东北大学弗雷德里克·C·戴维斯博士肯塔基州大学道格拉斯·G·麦克马洪博士我对感官体验如何形成和完善用于编码外部驱动的神经元活动的中枢神经系统的电路很感兴趣。在智力上，这个训练计划将提高我制定可检验的假设的能力，这些假设是关于驱动行为相关感觉加工背后的可塑性的细胞机制。从技术上讲，我将接受双光子成像和分析方面的培训，这些培训有助于在活组织中进行高分辨率的实时成像。我将接受使用细菌人工染色体技术的小鼠遗传学培训，以针对特定类型的细胞进行生理学研究和体内操作。这些技能将使我能够成功地实现我成为一名独立研究科学家的职业目标，并培训各个层次的学生学习神经生物学。未来的研究将在发育和行为状态的背景下，研究光或其他感官刺激对正在进行的基因表达动力学和神经元活动的影响。长期目标是更准确地定义生物体如何适应环境的细胞基础，以及当内部电路不能很好地适应时如何进行干预。李会[-1]I 19.姓名和学位(S)Z.黄之锋20.职位/职级助理教授研究兴趣/领域经验：神经营养素小鼠遗传学22.DES RcIPeTIOntrI.DsosnuotmexnceedusraocGpreov，nids%cde)understhaonwdexperiesnhcaepbersaifnunctioRn.ecesnttudiiensvisual皮质提示皮质内抑制回路的成熟对于启动和驱动关键时期的眼优势可塑性是必要的。然而，对所涉及的特定类型的抑制电路的成熟和调节尚不清楚。关键时期的可塑性也受到视觉剥夺和BDNF过度表达的调节，尽管其细胞机制尚不清楚。在这里，我们假设GABA能神经元的一个特定亚型--小白蛋白篮子中间神经元的功能成熟是关键时期陈词滥调的抑制机制的组成部分，并且是经验剥夺和BDNF调节的细胞靶点。我们将利用细菌人工染色体转基因(BAC)小鼠在PV中间神经元中表达GFP，利用双光子激光扫描显微镜和脑片电生理学来表征PV中间神经元的形态和生理发育。然后我们将研究暗培养对PV-中间神经元成熟的影响。最后，我们将使用在PV中间神经元中特异表达TrkB受体的显性阴性形式的BAC转基因小鼠，通过阻断TrkB信号来测试BDNF在PV中间神经元经验依赖性成熟中的作用。这些结果将揭示经验塑造已识别的抑制网络功能的机制，并提供强有力的证据，证明PV中间神经元回路的成熟有助于编码驱动眼优势可塑性所需的视觉信息。所获得的知识将有助于设计治疗癫痫和精神分裂症等疾病的药物治疗方法。PHS 416-1(12/98版)表第2页bb cc目录========================================Section End===========================================