Plasticity of Spinal Inhibition in Spinal Cord Injury

描述（由申请人提供）： 可以在GAD 67调节元件控制下表达GFP的转基因小鼠中鉴定GABA能神经元（奥利瓦（Oliva）等人，2000年）。全细胞斑片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可修饰性，将在有和没有慢性脊髓横断的小鼠中表征其内在和单胺能调节特性。将使用LCM对相同神经元群体进行平行DNA表达谱分析，以鉴定横切诱导的基因表达变化。总之，这些研究将确定GABA能中间神经元的生理和分子可塑性并将其相互关联。长期目标是确定参与脊髓抑制装置控制的基本分子和生理回路。在临床上，确定脊髓中GABA能神经元上的特定单胺能受体亚型以及它们的放电特性被调制的方式，应该确定用于选择性控制GABA能兴奋性的靶点。然后可以操纵这一点来限制被认为在各种疼痛状态和SCI后发生的椎板I中的增强的感觉传递。

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.