Modulation of motoneuronal acitivity by tonic inhibition in the spinal cord

运动指令由表达GABA(A)和甘氨酸受体的脊髓中间神经元控制。这些受体的激活在神经元水平上引起时相或紧张性抑制。初步数据显示，甘氨酸能紧张性抑制是抑制脊髓腹角自发动作电位活动的潜在机制。在这里，我们的目的是检验这一假设，即甘氨酸能或GABA能的紧张性抑制是否会转化为脊髓运动神经元活动的调节。为此，在器官型脊髓培养和急性脊髓切片中鉴定了表达GFP的转基因小鼠系(B6.Cg-TG(RP23-268L19-EGFP)2Mik/J)的运动神经元，并用细胞附着膜片钳技术测定了这些运动神经元的动作电位活性。此外，它的目的是确定紧张性抑制与自发运动神经元活动相比，对电和光解诱发的运动神经元事件的意义。最后，在器官型脊髓-骨骼肌共培养中，研究了甘草酸紧张性抑制对自发肌肉活动的影响。作为一个长期的结果，甘氨酸受体的调节可能是开发中枢作用的肌肉松弛药作为治疗下腰痛的新疗法的一个有价值的药理学工具。

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.