Plasticity of Spinal Inhibition in Spinal Cord Injury

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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.