Modulation of motoneuronal acitivity by tonic inhibition in the spinal cord

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Locomotoric commands are controlled by spinal interneurons expressing GABA(A)- and glycine-receptors. The activation of these receptors induces a phasic or tonic inhibition at a neuronal level. Preliminary data revealed that a glycinergic tonic inhibition is the underlying mechanism for depression of spontaneous action potential activity in the spinal ventral horn. Here we aim to test the hypothesis whether a glycinergic or GABAergic tonic inhibition translates into a modulation of spinal motoneuronal activity. For this purpose GFP-expressing motoneurons of a transgenic mouse line (B6.Cg-Tg(RP23-268L19-EGFP)2Mik/J) are identified in organotypic spinal cultures and acute spinal slices and the action potential activity of these motoneurons is determined by a cell-attached patch-clamp technique. Additionally, it is aimed to determine the significance of tonic inhibition on electrically and photolytically evoked motoneuronal events in contrast to spontaneous motoneuronal acitivity. Eventually, the effect of a glycinerigc tonic inhibition on spontaneous muscle activity is investigated in an organotypic spinal cord-skeletal muscle coculture. As a long-term result, modulation of glycine receptors might be a valuable pharmacologic tool for the development of centrally acting muscle relaxants as a novel therapy for low back pain.