Interneuronal mechanisms for the control of walking

描述（由申请人提供）：截瘫患者梦想在脊髓损伤后能够再次行走。一个实际的问题是是否有可能重新激活剩余的脊髓神经回路来控制一些失去的运动功能。了解中间神经元的特性和它们在脊髓回路中的相互作用对于释放这种潜能至关重要。因此，本研究的重点是最近发现的泥鳅屈肌和伸肌中心的中间神经元对行走的控制。具体目的是确定这些特殊区域的中间神经元，这些中间神经元是产生行走的候选起搏器或移行细胞，确定这些细胞的膜特性，确定通过间隙连接通道产生运动样活动的电和代谢耦合的作用，并确定从感觉传入通路到这些中间神经元的突触投射模式。在体外泥狗脊髓-前肢制备过程中，细胞内记录由谷氨酸或其激动剂NMDA诱导的四肢类行走运动。四类中间神经元将被识别的标准组合，并基于它们的放电模式，与肘屈肌和伸肌的相活动。将对每种类型的细胞进行电生理学和组织学检查。其目标是揭示支配行走的神经回路的组织和运作的共同原则。从这项研究中得到的将是与行走产生相关的每一种已识别的中间神经元的不同感觉投射的详细图像。它还将确定是否有一群中间神经元在脊髓运动回路中起起搏器细胞的作用。尽管这项研究的重点是运动回路的基本神经科学，但在考虑如何在临床上利用脊髓损伤后残留的任何人类中枢模式发生器之前，这些信息是必不可少的。

DESCRIPTION (provided by applicant): Paraplegic patients dream to be able to walk again after spinal cord injuries. A practical issue concerns the feasibility to reactivate the spared spinal neural circuitry to control some of the lost locomotor functions. It is critical to understand the properties of interneurons and their interactions within the spinal circuitry in order to unlock this potential. This study thus focuses on the control of walking by interneurons within the recently identified flexor and extensor centers of the mudpuppy (Necturus Maculatus). The specific aims are to identified interneurons in these specialized regions that are candidate pacemaker or transitional cells for the generation of walking, to determine the membrane properties of these cells, to determine the role of electrical and metabolic coupling through gap junction channels in the generation of locomotor-like activity, and to determine the pattern of synaptic projections from sensory afferent pathways to these interneurons. Intracellular recording will be performed in the in vitro mudpuppy spinal cord-forelimb preparation during walking-like movement of the limbs induced by bath application of glutamate or its agonist NMDA. Four classes of interneurons will be identified by a combination of criteria and based on their firing pattern in relation to the phasic activity of the elbow flexor and extensor muscles. Each type of cells will be examined electrophysiologically and histologically. The goals are to unravel common principles that govern the organization and operation of the neural circuitry for walking. What will emerge from this study is a detailed picture of differential sensory projections to each type of identified interneurons associated with the generation of walking. It will also be determined whether there is a population of interneurons that function as pacemaker cells in the spinal cord locomotor circuitry. Although this investigation focuses on the basic neuroscience of the locomotor circuitry, this information is essential before considering how one can utilize clinically whatever human central pattern generator remains after spinal cord injury.