Control of Efferent and Afferent Peripheral Nerve Activity with Intrafascicular Microstimulation

[134545] normann .本研究的重点是麻醉猫科动物阴部神经束轴突的电生理研究。它的动机是最近开发的高电极计数微电极阵列，如犹他倾斜电极阵列(以下简称，？犹他州数组吗?)Utah阵列可以被插入周围神经系统的束内，以选择性地刺激束内的小群轴突。这种不断发展的技术在选择性控制远端肌肉组织方面的局限性尚未得到充分探讨，这为提出的工作提供了动力。低频刺激，通过单个微电极在犹他州阵列植入猫坐骨神经筋膜内，可以选择性地激活动物的九块肌肉。S后肢。通过Utah阵列中的微电极进行高频交流电刺激可以选择性地阻断坐骨神经的正侧神经活动，从而选择性地阻断目标肌肉的激活。这些研究没有优化刺激参数以产生长时间的选择性兴奋或远端肌肉组织阻滞，也没有将刺激位点定位到特定的神经束或单个神经束内的轴突亚群。最后，直立动作电位的阻断与阻断前肌肉收缩的短暂性增加有关，而可能减少这种短暂性收缩的刺激方案尚未研究。这项工作将研究猫阴部神经束内微电极刺激的局限性，使用最近开发的犹他阵列，该阵列专门设计用于改善对该神经轴突的访问。与传统的犹他阵列相比，这种新设计的电极间距为200微米，植入猫阴部神经的电极空间密度增加了四倍。这项工作主要集中在猫阴部神经上，因为它有传入和传出纤维在单个神经束内运行，这将允许研究在单个神经束内同时激发传入和阻断传出轴突亚群的可行性。此外，激活和阻断单束轴突的后果具有易于监测的特定运动后果：传入纤维的激活引起膀胱壁（逼尿肌）的反射性收缩，而传出纤维的激活将引起尿道外括约肌的肌电图。这些后一轴突将成为阻断正态动作电位的目标，从而产生受控的括约肌松弛。提出的工作还将利用犹他阵列中电极尖端的精确几何位置，并允许绘制该神经的功能组织，其中包括涉及反射性膀胱收缩、反射性勃起、外尿道和肛门括约肌收缩的神经元通路。

1134545NormannThe proposed work is focused on electrophysiological studies of the axons in the fascicles of the pudendal nerve of anesthetized felines. It is motivated by recently developed high-electrode-count microelectrode arrays, such as Utah Slanted Electrode Arrays (hereafter, ?Utah arrays?). Utah arrays can be inserted intrafascicularly into the peripheral nervous system to selectively stimulate small groups of axons within the fascicles. The limitations of this evolving technology on the selective control of distal musculature have not been fully explored, which provides the motivation for the proposed work. Low frequency stimuli, delivered via individual microelectrodes in a Utah array implanted intrafascicularly into the feline sciatic nerve can selectively activate up to nine muscles of the animal?s hind limb. High frequency alternating current stimulation via microelectrodes in a Utah array can selectively block orthodromic neural activity in the sciatic nerve, and thereby, selectively block activation of a targeted muscle. These studies did not optimize the stimulation parameters to produce prolonged selective excitation or blocking of distal musculature, nor did they localize the stimulation sites to particular fascicles, or to axon subsets within individual fascicles. Finally, the blocking of orthodromic action potentials was associated with a transient increase in muscular contraction preceding the block, and stimulation protocols that may reduce this transient onset contraction were not investigated. The proposed work will investigate these limitations of intrafascicular microelectrode stimulation in the feline pudendal nerve using a recently developed Utah array that was designed specifically to provide improved access to the axons of this nerve. Compared to a conventional Utah array, this new design has electrodes spaced at 200 microns and provides a four-fold increase in the spatial density of the electrodes implanted into the feline pudendal nerve. The proposed work is focused on the feline pudendal nerve because it has afferent and efferent fibers running within a single fascicle which will allow the investigation of the feasibility of simultaneous excitation of afferent and blocking of efferent axonal subsets within a single fascicle. Further, the consequences of activation and blocking the axons in this single fascicle have specific motor consequences that are readily monitored: activation of the afferent fibers evokes a reflexive contraction of the bladder wall (the detrusor muscle), and activation of the efferent fibers will evoke electromyograms in the external urethral sphincter. These latter axons will be targeted for blocking of orthodromic action potentials, thereby, producing controlled relaxation of the sphincter. The proposed work will also take advantage of the precise geometric location of the electrode tips in the Utah array and allow mapping of the functional organization of this nerve, which includes neuronal pathways involved in reflexive bladder contractions, reflex erection, and contraction of the external urethral and anal sphincters.