Controlling specific locomotor behaviors through multidimensional monoaminergic modulation of spinal circuitries.
Controlling specific locomotor behaviors through multidimensional monoaminergic modulation of spinal circuitries.
复制标题
通过脊髓回路的多维单胺能调节来控制特定的运动行为。
DOI：
10.1523/jneurosci.5796-10.2011
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发表时间：
2011-06-22
期刊：
影响因子：
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通讯作者：
Courtine G
中科院分区：
文献类型：
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作者：
Musienko P;van den Brand R;Märzendorfer O;Roy RR;Gerasimenko Y;Edgerton VR;Courtine G
下行单胺能输入显着影响脊髓运动回路，但特定的受体和步行行为的控制之间的功能关系仍然知之甚少。为了确定这些相互作用，我们操纵多巴胺能，多巴胺能和去甲肾上腺素能神经通路的运动过程中，使电脊髓刺激在成年脊髓大鼠体内。使用先进的神经生物力学记录和多维统计程序，我们发现，每个单胺能受体调制广泛但不同的频谱的运动，动力学和EMG特性，我们表示成受体特异性的功能地图。然后，我们利用这一目录的单胺能调谐功能，设计最佳的药理学组合，以鼓励瘫痪大鼠的运动。我们发现，在大多数情况下，受体特异性调制的影响，同时刺激多个通路时，总结近代数。利用这些预测的相互作用，我们阐述了一个多维的单胺能干预，恢复协调后肢运动与正常水平的负重和部分平衡维持脊髓大鼠。这些研究结果提供了新的观点的功能和脊髓单胺能受体系统之间的相互作用，在生产步进，并定义了一个框架，以定制药物治疗改善中枢神经系统疾病后的神经功能。
Descending monoaminergic inputs markedly influence spinal locomotor circuits, but the functional relationships between specific receptors and the control of walking behavior remain poorly understood. To identify these interactions, we manipulated serotonergic, dopaminergic, and noradrenergic neural pathways pharmacologically during locomotion enabled by electrical spinal cord stimulation in adult spinal rats in vivo. Using advanced neurobiomechanical recordings and multidimensional statistical procedures, we reveal that each monoaminergic receptor modulates a broad but distinct spectrum of kinematic, kinetic and EMG characteristics, which we expressed into receptor–specific functional maps. We then exploited this catalogue of monoaminergic tuning functions to devise optimal pharmacological combinations to encourage locomotion in paralyzed rats. We found that, in most cases, receptor-specific modulatory influences summed near algebraically when stimulating multiple pathways concurrently. Capitalizing on these predictive interactions, we elaborated a multidimensional monoaminergic intervention that restored coordinated hindlimb locomotion with normal levels of weight bearing and partial equilibrium maintenance in spinal rats. These findings provide new perspectives on the functions of and interactions between spinal monoaminergic receptor systems in producing stepping, and define a framework to tailor pharmacotherapies for improving neurological functions after CNS disorders.