Parvalbumin containing interneuron connectivity and critical period modulation

含有中间神经元连接和关键期调节的小白蛋白

• 批准号: 7395168
• 负责人: Marc Nahmani
• 金额: $ 1.15万
• 依托单位: UNIVERSITY OF VIRGINIA
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-03-01 至 2008-08-12
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7395168
• 关键词: Acceleration; Accounting; Acids; Address; Adult; Albumins; Axon; Brain; Cells; Chromosome Pairing; Chronic; Closure; Condition; Coupled; Data; Dendrites; Development; Diazepam; Electrophysiology (science); Engineering; Event; Evoked Potentials; GABA Agonists; Gap Junctions; Glutamates; Green Fluorescent Proteins; Height; Immunoelectron Microscopy; Infusion procedures; Interneurons; Label; Laboratory Finding; Measures; Modeling; Modification; Mus; Neurons; Ocular Dominance; Operative Surgical Procedures; Pan Genus; Parvalbumins; Pharmaceutical Preparations; Physiological; Physiology; Play; Population; Prohibit; Property; Pyramidal Cells; Role; Sensory; Sensory Deprivation; Staining method; Stains; Synapses; Testing; Thalamic structure; Therapeutic; Time; Transgenic Mice; Visual; Visual Cortex; area striata; connexin 36; critical developmental period; enhanced green fluorescent protein; gamma-Aminobutyric Acid; monocular; monocular deprivation; neuronal cell body; osmotic minipump; prevent; promoter; protein expression; research study; stellate cell; therapeutic target; transmission process

DESCRIPTION (provided by applicant): Only sensory deprivation confined to a small developmental time window can alter the physiology and neuronal connectivity subserving ocular dominance in visual cortex. Following this period, the potential for dramatic reorganization is lost. GABAergic inhibition plays a permissive role in allowing for the onset of this 'critical period' plasticity, in addition to its probable involvement in critical period closure. Yet the specific subtype(s) of GABAergic neurons involved, and the mechanisms whereby they prevent ocular dominance plasticity have not been determined. Recent studies and preliminary data suggest that pan/albumin containing GABAergic interneurons are poised to play a key role in critical period modulation. This project aims to examine the role of pan/albumin interneuron connectivity during and after the critical period, in order to enhance our understanding of the structural events that eventually constrain ocular dominance plasticity. Furthermore, the long-term objective is to provide a detailed account of how inhibitory inputs are consolidated during developmental plasticity, to elucidate the conditions necessary to reinstitute cortical plasticity for possible therapeutic advantage. Pan/albumin interneurons receive nearly all the input from primary sensory thalamic axons to GABAergic circuitry in adult visual cortex. Moreover, their abundant gap junctions with one another throughout development may allow for widespread inhibitory control of specific excitatory cortical networks. These experiments seek to determine whether parvalbumin interneuron synapses to glutamatergic and GABAergic neuron subtypes in visual cortex are 'pruned' over the critical period, and the extent to which the maturation of these connections is accelerated following the GABAergic induction of premature critical period closure. The development of parvalbumin interneuron connectivity will be characterized using a line of GFP-parvalbumin mice, in conjunction with immuno-electron microscopy and chronic drug infusion. In addition, these studies will employ monocular deprivation and visually evoked potentials to assess whether increased cortical GABAergic activity and a precocious critical period closure is accompanied by a similarly premature consolidation of parvalbumin interneuron contacts.

描述（由申请人提供）： 只有局限于较小的发育时间窗口的感觉剥夺才能改变生理学和神经元连接，从而维持视觉皮层中眼睛的主导地位。在此时期之后，戏剧性重组的潜力就消失了。 GABA 能抑制除了可能参与关键期的关闭之外，还在允许这一“关键期”可塑性的开始方面发挥着许可作用。然而，所涉及的 GABA 能神经元的具体亚型以及它们阻止眼部优势可塑性的机制尚未确定。最近的研究和初步数据表明，含有 GABA 能中间神经元的泛/白蛋白有望在关键期调节中发挥关键作用。该项目旨在研究关键期期间和之后泛/白蛋白中间神经元连接的作用，以增强我们对最终限制眼优势可塑性的结构事件的理解。此外，长期目标是详细说明抑制输入在发育可塑性过程中如何巩固，以阐明重新建立皮质可塑性以获得可能的治疗优势所需的条件。泛/白蛋白中间神经元接收从初级感觉丘脑轴突到成人视觉皮层 GABA 电路的几乎所有输入。此外，在整个发育过程中，它们之间丰富的间隙连接可能允许对特定兴奋性皮层网络进行广泛的抑制控制。这些实验旨在确定视觉皮层中谷氨酸能和 GABA 能神经元亚型的小白蛋白中间神经元突触是否在关键期被“修剪”，以及在 GABA 能诱导关键期过早关闭后这些连接的成熟加速程度。小白蛋白中间神经元连接的发展将使用一系列 GFP-小白蛋白小鼠，结合免疫电子显微镜和长期药物输注来表征。此外，这些研究将采用单眼剥夺和视觉诱发电位来评估皮质 GABA 活性的增加和过早的关键期关闭是否伴随着小白蛋白中间神经元接触的类似过早巩固。