Critical period in visual cortex: inhibitory circuits

18. 葛底斯堡学院斯普林斯-福特区菲尼克斯维尔区东北大学弗雷德里克·C·戴维斯博士肯塔基大学道格拉斯·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回路很感兴趣。在智力上，这个训练计划将提高我制定可测试假设的能力，这些假设是关于驱动行为相关感觉处理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，这对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方面的培训，使用细菌人工染色体技术针对特定的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地实现我的职业目标，成为一名独立的研究科学家，培养各级神经生物学的学生。未来的研究将研究光或其他感官刺激对发育和行为状态下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，以及当内部电路不适应时如何进行干预。李津[1]我19岁。姓名及学位：黄志强职位/职衔助理教授研究方向/方向：经验依赖性神经营养因子小鼠遗传学DES RcIPeTIOntrI.DsosnuotmexnceedusraoceGpreov nids % understhaonwdexperiesnhcaepbersaifnunctioRn cde)。视觉皮层发育表明，在关键时期，皮层内抑制回路的成熟对于启动和驱动眼优势可塑性是必要的。然而，所涉及的特定类型的抑制回路的成熟和调节尚不清楚。尽管细胞机制尚不清楚，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能神经元的一个特定亚型，小白蛋白（Pv）篮中间神经元的功能成熟是关键时期可塑性抑制机制的一个组成部分，也是经验剥夺和BDNF调节的细胞靶点。以表达GFP的细菌人工染色体转基因（BAC）小鼠pv -中间神经元为研究对象，利用双光子激光扫描显微镜和脑电生理切片对pv -中间神经元的形态和生理发育进行了研究。然后，我们将研究暗育对pv -中间神经元成熟的影响。最后，我们将利用BAC转基因小鼠在pv -中间神经元中特异性表达trkB受体的显性阴性形式，通过阻断trkB信号传导，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促进了驱动眼优势可塑性所需的视觉信息编码。所获得的知识将有助于设计疾病状态（如癫痫和精神分裂症）的药物治疗。小灵通416 - 1(启12/98)表单页面2 BB cc目录 ======================================== 节结束 ===========================================

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===========================================