Modulation of motoneuronal acitivity by tonic inhibition in the spinal cord

通过脊髓强直抑制调节运动神经元活动

• 批准号: 261249808
• 负责人: Professor Dr. Bernd Antkowiak, since 3/2016
• 金额: --
• 依托单位: Sektion für Experimentelle Anästhesiologie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2014
• 资助国家: 德国
• 起止时间: 2013-12-31 至 2018-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/261249808?language=en
• 关键词: Modulation; motoneuronal; acitivity; tonic; inhibition

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.

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诱导阶段性或强直性抑制。初步数据显示，甘氨酸能紧张性抑制是脊髓腹角自发动作电位活动抑制的潜在机制。在这里，我们的目的是测试的假设是否甘氨酸或GABA能紧张性抑制转化为脊髓运动神经元活动的调制。为此目的，在器官型脊髓培养物和急性脊髓切片中鉴定转基因小鼠系（B6.Cg-Tg（RP 23 - 268 L19-EGFP）2 Mik/J）的GFP表达运动神经元，并通过细胞附着膜片钳技术测定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的电和光诱发的运动神经元事件的意义，而自发运动神经元活性。最后，在器官型脊髓-骨骼肌共培养物中研究甘氨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一个有价值的药理学工具，中枢作用的肌肉松弛剂作为一种新的治疗腰痛的发展。