Effects of Sympathetic Nerve Activity

描述（由申请人提供）： 精细运动技能的表现是具有挑战性的老年退伍军人视力丧失。眼手协调和感觉输入的整合对于执行精细运动技能至关重要。衰老导致感觉输入减少，并且通常伴有视力和运动控制受损。缺乏有效的康复策略，为老年退伍军人视力丧失，需要开发，以提高适应能力的神经系统（可塑性）在运动学习。拟议项目的长期目标是帮助为视力丧失的老年退伍军人开发创造性的康复干预措施和辅助技术。然而，首先需要确定有效的干预措施，这将导致在健康的年轻人精细运动技能学习过程中增强神经可塑性。运动皮层中的神经可塑性通过兴奋性N-甲基-D-天冬氨酸（NMDA）通路的激活而强烈增强，并通过抑制性γ-氨基丁酸（GABA）的激活而抑制。虽然在药理学研究中已经提出了NMDA能和GABA能功能的调节，但尚不清楚生理分泌的单胺是否通过增强的交感神经活性来调节这些功能。我们最近发现，生理上增强的交感神经活动调节神经活动，以便用手部肌肉执行精确任务。特别是，我们的初步观察表明，生理上提高交感神经活动可以增强运动皮层皮层内的促进（由NMDA介导）和减少运动皮层内抑制（由GABA介导）。具体目标：研究手部肌肉放松和执行精确任务时，交感神经生理活动增强对运动皮层内抑制和易化的影响。假设：由于GABA能功能抑制和NMDA能功能增强，运动皮质皮质内抑制被解除，皮质内易化随着交感神经活动的生理增强而增强（该假设得到我们初步数据的支持）。参见第3-4节）。确定干预的生理预测因子有助于确定最佳受益于干预的个体。这可能导致基于交感神经系统和神经肌肉系统之间的相互作用的新的康复策略的发展

DESCRIPTION (provided by applicant): Performance of fine motor skills is challenging for aging veterans with vision loss. Eye-hand coordination and integration of sensory input is essential to perform fine motor skills. Aging leads to reduced sensory input and is often accompanied by impaired vision and movement control. Efficient rehabilitation strategies for aging veterans with vision loss are lacking and need to be developed to enhance the adaptive capacity of the nervous system (plasticity) during motor learning. The long-term objectives of the proposed project are to help develop creative rehabilitative interventions and assistive technologies for aging veterans with vision loss. However, it is first necessary to identify effective interventions that would lead to enhancing neural plasticity during fine motor skill learning in healthy young adults. Neural plasticity in the motor cortex is strongly enhanced by the activation of excitatory N-methyl-D-aspartate (NMDA) pathways and inhibited by the activation of inhibitory gamma-aminobutyric acid (GABA). Although modulations of NMDAergic and GABAergic functions have been suggested in pharmacological studies, it is unknown whether physiologically secreted monoamines modulate these functions with heightened sympathetic nerve activity. We have recently found that physiologically heightened sympathetic nerve activity modulates neural activity for fine performance of precision tasks with a hand muscle. In particular, our preliminary observations suggested that physiologically heightened sympathetic nerve activity could enhance motor cortex intracortical facilitation (mediated by NMDA) and reduce motor cortex intracortical inhibition (mediated by GABA). Specific Aim: To examine the effects of physiologically heightened sympathetic nerve activity on motor cortex intracortical inhibition and facilitation when a hand muscle is relaxed and performing a precision task. Hypothesis: Motor cortex intracortical inhibition is disinhibited and intracortical facilitation is enhanced with physiologically heightened sympathetic nerve activity due to inhibited GABAergic functions and enhanced NMDAergic functions (The hypothesis is supported by our preliminary data. See Section 3-4). The identification of physiologic predictors for an intervention can help to target those individuals who best benefit from the intervention. This could lead to the development of new rehabilitative strategies based on the interactions between the sympathetic nervous system and the neuromuscular system