Critical period in visual cortex: inhibitory circuits

18.奖学金培训和职业目标机构/公司主管雇主葛底斯堡学院Spring-Ford Dist.菲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麦克马洪博士我着迷于感觉经验如何形成和完善中枢神经系统的电路，用于编码外部驱动的神经元活动。在智力上，这个训练计划将提高我的能力，以制定可测试的假设有关的细胞机制，驱动可塑性的行为相关的感觉处理。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的小鼠遗传学培训。这些技能将使我能够成功地在我的职业目标，成为一个独立的研究科学家，并培养学生在神经生物学的各个层次。 未来的研究将研究光或其他感官刺激对发育和行为状态背景下正在进行的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，以及如何在内部电路不适应时进行干预。-li'll [-1”]i 19.姓名和学位Z. 20.第二十三章21.第二十一章.研究兴趣/领域经验-视皮层内抑制回路的成熟对于在关键期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。关键期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，我们假设一个特定的GABA能神经元亚型，小白蛋白（PV）篮中间神经元的功能成熟，是关键期可塑性的抑制机制的一个组成部分，和经验剥夺和BDNF调节的细胞靶点。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BDNF在PV-中间神经元的经验依赖性成熟中的作用，通过使用在PV-中间神经元中特异性表达trkB受体的显性阴性形式的BAC转基因小鼠阻断trkB信号传导。这些结果将揭示一种机制，通过这种机制，经验的形状功能的一个确定的抑制网络，并提供强有力的证据，成熟的PV-interneuron电路促进编码的视觉信息，必要的驱动眼优势可塑性。所获得的知识将有助于设计药物治疗疾病状态，如癫痫和精神分裂症。PHS 416-1（12/98修订版）表格第2页BB cc目录==

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