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. 奖学金培训和职业机构/公司主管雇主的目标葛底斯堡学院斯普林-福特区。菲尼克斯维尔区东北大学 Frederick C Davis 博士 东北大学 Frederick C Davis 博士 肯塔基大学 Douglas G McMahon 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回路非常着迷。从智力上讲，这个培训计划将增强我针对细胞机制制定可检验假设的能力，这些细胞机制驱动行为相关感官处理的可塑性。从技术上讲，我将接受 2 光子成像和分析方面的培训，这对于活体组织的高分辨率实时成像很有用。我将接受小鼠遗传学培训，使用细菌人工染色体技术针对特定细胞类型进行生理研究和体内操作。这些技能将使我能够成功实现成为一名独立研究科学家的职业目标，并培训神经生物学各个级别的学生。 未来的研究将探讨光或其他感官刺激对发育和行为状态下持续基因表达动态和神经元活动的影响。长期目标是更精确地定义生物体如何适应环境的细胞基础，以及当内部回路不能很好适应时如何进行干预。 -li'll[-1"]i 19. 姓名和学位 Z. Josh Huang 20. 职位/级别 助理教授 21. 研究兴趣/领域 经验-d _ependent p]astJcity 神经营养蛋白 小鼠 _遗传学 22.DES RcIPeTIOntrI.DsosnuotmexceedusraoceGpreov,nids%cde)understhaonwdexperiesnhcaepbersaifnunctioRn.ecesnttudiiens 视觉皮层表明，皮质内抑制回路的成熟对于在关键时期启动和驱动眼优势可塑性是必要的。然而，具体类型的成熟和监管 所涉及的抑制电路尚不清楚。尽管细胞机制仍不清楚，但关键期可塑性也受到视觉剥夺和 BDNF 过度表达的调节。在这里，我们假设 GABA 能神经元的特定亚型（小清蛋白 (Pv) 篮子中间神经元）的功能成熟是关键期普拉性潜在抑制机制的组成部分，也是体验的细胞目标 剥夺和 BDNF 调节。使用在 Pv 中间神经元中表达 GFP 的细菌人工染色体转基因 (BAC) 小鼠，我们将使用双光子激光扫描显微镜和脑切片中的电生理学来表征 Pv 中间神经元的形态和生理发育。然后我们将研究黑暗饲养对 Pv 中间神经元成熟的影响。最后，我们将测试 使用 BAC 转基因小鼠，特别是在 Pv 中间神经元中表达显性失活形式的 trkB 受体，通过阻断 trkB 信号传导，BDNF 在 Pv 中间神经元的经验依赖性成熟中的作用。这些结果将揭示一种机制，通过该机制，经验塑造已识别的抑制网络的功能，并提供强有力的证据，证明 Pv 中间神经元回路的成熟促进了驱动眼优势所需的视觉信息的编码 可塑性。获得的知识将有助于设计针对癫痫和精神分裂症等疾病的药物治疗。 PHS 416-1（修订版 12/98）表格第 2 页 BB cc 目录 ============================================ 部分 结束=============================================