Plasticity of Spinal Inhibition in Spinal Cord Injury

描述(由申请人提供)： 在GAD67调控元件的控制下，可以在表达GFP的转基因小鼠中鉴定出GABA能神经元(Oliva等人，2000年)。全细胞膜片记录允许表征视觉识别的GABA能神经元的固有膜特性。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身上表征它们的内在和单胺能调节特性。使用LCM对同一组神经元进行并行DNA表达谱分析，以识别横切诱导的基因表达变化。总之，这些研究将确定并相互关联已识别的GABA能中间神经元的生理学和分子可塑性。长期目标是确定参与控制脊髓抑制装置的基本分子和生理回路。临床上，识别脊髓GABA能神经元上的特异性单胺受体亚型及其放电特性的调节方式应确定选择性控制GABA能兴奋性的靶点。然后可以操纵这一点，以限制I层中增强的感觉传递，这种感觉传递被认为发生在各种疼痛状态和脊髓损伤后。

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.