Plasticity of Spinal Inhibition in Spinal Cord Injury

脊髓损伤中脊髓抑制的可塑性

• 批准号: 6836863
• 负责人: Kimberly J Dougherty
• 金额: $ 2.54万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-08-09 至 2006-08-08
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6836863
• 关键词: animal tissue; cell population study; electrophysiology; gamma aminobutyrate; gene expression; gene expression profiling; genetic regulation; genetically modified animals; interneurons; laboratory mouse; laser capture microdissection; microarray technology; nervous system regeneration; neural information processing; neural inhibition; neural plasticity; neurochemistry; neurogenetics; neuroregulation; pain; predoctoral investigator; protein structure function; somesthetic sensory cortex; spinal cord injury; voltage gated channel

DESCRIPTION (provided by applicant): GABAergic neurons can be identified in transgenic mice expressing GFP under the control of a GAD67 regulatory element (Oliva et al., 2000). Whole-cell patch recordings permit characterization of the intrinsic membrane properties of visually-identified GABAergic neurons. To study the modifiability of these neurons, their intrinsic and monoaminergic modulatory properties will be characterized in mice with and without chronic spinal transection. Parallel DNA expression profiling of the same population of neurons with LCM will be performed to identify transection-induced alterations in gene expression. Together, these studies will identify and inter-relate physiologic and molecular plasticity in identified GABAergic interneurons. The long-term goal is to identify fundamental molecular and physiological circuits engaged in the control of the spinal inhibitory apparatus. Clinically, identification of the specific monoaminergic receptor subtypes on GABAergic neurons in the spinal cord and the way in which their firing properties are modulated should identify targets for selective control of GABAergic excitability. This can then be manipulated to limit enhanced sensory transmission in lamina I that is thought to occur in various pain states and after SCI.

描述（由申请人提供）： 可以在GAD67调节元件的控制下表达GFP的转基因小鼠中鉴定GABA能神经元（Oliva等，2000）。全细胞斑块记录允许表征视觉识别的GABA能神经元的内在膜特性。为了研究这些神经元的修改性，它们的内在和单胺能调节特性将在有和没有慢性脊柱横断的小鼠中进行表征。将进行与LCM的同一神经元群体的平行DNA表达分析，以鉴定基因表达的横断诱导的改变。这些研究将共同​​确定鉴定出的GABA能中间神经元中的生理和分子可塑性。长期的目标是确定从事脊柱抑制剂控制的基本分子和生理回路。在临床上，识别脊髓中GABA能神经元的特异性单胺能受体亚型以及调节点火特性的方式应识别靶标，以选择性控制GABAergic兴奋性。然后可以操纵这以限制椎板I中的增强感觉传播，这种传播被认为是在各种疼痛状态和SCI之后发生的。