Metaplasticity within the spinal cord: Evidence brain-derived neurotrophic factor (BDNF), tumor necrosis factor (TNF), and alterations in GABA function (ionic plasticity) modulate pain and the capacity to learn.
Metaplasticity within the spinal cord: Evidence brain-derived neurotrophic factor (BDNF), tumor necrosis factor (TNF), and alterations in GABA function (ionic plasticity) modulate pain and the capacity to learn.
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DOI：
10.1016/j.nlm.2018.04.007
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发表时间：
2018-10
影响因子：
2.7
通讯作者：
Huang YJ
中科院分区：
文献类型：
--
作者：
Grau JW;Huang YJ
有证据表明，行为训练和神经损伤可以参与调节适应性潜力的化生过程。这个问题是探讨在一个模型系统，探讨如何训练影响学习的能力，在较低的（腰骶）脊髓。脊髓横断尾侧施加反应相关（可控）刺激诱导指示学习的行为改变。这种行为变化在以不可控制的方式接受刺激的动物中没有观察到。暴露于无法控制的刺激也会使脊髓学习能力丧失24-48小时。可控刺激具有相反的效果;它参与了一个能够学习的过程，并防止/逆转了由不可控刺激引起的学习缺陷。这些观察结果表明，学习事件可以影响在未来情况下的学习能力，提供了一个行为元可塑性的例子。可控刺激的保护/恢复作用与脑源性神经营养因子（BDNF）的上调有关。学习的中断与疼痛（伤害性）回路的敏感化有关，这是通过减少GABA依赖性抑制实现的。脊髓损伤（SCI）后，调节Cl-外流的协同转运蛋白（KCC 2）下调。这导致细胞内Cl-浓度增加，减少（并可能逆转）Cl-通过GABA-A受体的内向流动。GABA功能的转变（离子可塑性）增加了损伤尾侧的神经兴奋性，并为伤害性敏化奠定了基础。损伤诱导的KCC 2的变化与下行性多巴胺能（5 HT）纤维的丢失有关，该纤维通过5 HT-1A受体调节脊髓背角内的可塑性。有证据表明，这些改变脊髓可塑性影响疼痛的大脑依赖的任务（地方条件反射）。研究结果表明，离子可塑性可以影响学习潜力，将神经回路从阻尼/硬连线转变为兴奋/塑性。
Evidence is reviewed that behavioral training and neural injury can engage metaplastic processes that regulate adaptive potential. This issue is explored within a model system that examines how training affects the capacity to learn within the lower (lumbosacral) spinal cord. Response-contingent (controllable) stimulation applied caudal to a spinal transection induces a behavioral modification indicative of learning. This behavioral change is not observed in animals that receive stimulation in an uncontrollable manner. Exposure to uncontrollable stimulation also engages a process that disables spinal learning for 24-48 hrs. Controllable stimulation has the opposite effect; it engages a process that enables learning and prevents/reverses the learning deficit induced by uncontrollable stimulation. These observations suggest that a learning episode can impact the capacity to learn in future situations, providing an example of behavioral metaplasticity. The protective/restorative effect of controllable stimulation has been linked to an up-regulation of brain-derived neurotrophic factor (BDNF). The disruption of learning has been linked to the sensitization of pain (nociceptive) circuits, which is enabled by a reduction in GABA-dependent inhibition. After spinal cord injury (SCI), the co-transporter (KCC2) that regulates the outward flow of Cl- is down-regulated. This causes the intracellular concentration of Cl- to increase, reducing (and potentially reversing) the inward flow of Cl- through the GABA-A receptor. The shift in GABA function (ionic plasticity) increases neural excitability caudal to injury and sets the stage for nociceptive sensitization. The injury-induced shift in KCC2 is related to the loss of descending serotonergic (5HT) fibers that regulate plasticity within the spinal cord dorsal horn through the 5HT-1A receptor. Evidence is presented that these alterations in spinal plasticity impact pain in a brain-dependent task (place conditioning). The findings suggest that ionic plasticity can affect learning potential, shifting a neural circuit from dampened/hard-wired to excitable/plastic.
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