Trasande Caitlin Aptowicz, Ramirez Jan-Marino
Committee on Neurobiology, Department of Organismal Biology and Anatomy, The University of Chicago, Chicago, Illinois, USA.
J Clin Neurophysiol. 2007 Apr;24(2):154-64. doi: 10.1097/WNP.0b013e318033787f.
Neural networks operate robustly despite destabilizing factors, ranging from gene product turnover to circuit refinement, throughout life. Maintaining functional robustness of neuronal networks critically depends upon forms of homeostatic plasticity including synaptic scaling. Synaptic strength and intrinsic excitability have been shown to "scale" (up or down) in response to altered ambient activity levels, and this has led to the general idea that homeostatic plasticity operates along a continuum. After 48 hours of activity deprivation, cultured hippocampal networks exhibited a homeostatic-type reconfiguration that was discrete: a switch from spontaneous spiking to oscillatory bursting. Blockade of fast glutamatergic and GABAergic transmission abolished spontaneous network bursting, but the majority of neurons exhibited intrinsic bursting in response to current injection, which was not the case in control tissue. This de novo intrinsic bursting could be blocked by cadmium chloride, suggesting that this bursting involves calcium mechanisms. Immunohistochemistry confirmed that activity-deprived slice cultures exhibited a widespread upregulation of voltage-dependent calcium channels compared with controls. Calcium imaging studies from activity-deprived slices demonstrated that spontaneous bursting was not a local behavior, but rather a global, synchronous phenomenon, reminiscent of seizure activity. These data suggest that the input/output transformation of individual neurons undergoing homeostatic remodeling is more complex than simple scaling. Network consequences of this transformation include network destabilization of epileptic proportions. Spontaneous activity plays a critical role in actively maintaining homeostatic balance in networks, which is lost after activity deprivation.
神经网络在整个生命过程中，尽管存在从基因产物更新到电路细化等各种不稳定因素，仍能稳健运行。维持神经网络的功能稳健性关键取决于包括突触缩放在内的稳态可塑性形式。突触强度和内在兴奋性已被证明会根据环境活动水平的改变而“缩放”（上调或下调），这导致了稳态可塑性沿连续体运作的普遍观点。在48小时的活动剥夺后，培养的海马体网络表现出一种离散的稳态型重构：从自发尖峰放电转变为振荡爆发。快速谷氨酸能和GABA能传递的阻断消除了自发网络爆发，但大多数神经元在电流注入时表现出内在爆发，而对照组织中并非如此。这种新生的内在爆发可被氯化镉阻断，表明这种爆发涉及钙机制。免疫组织化学证实，与对照相比，活动剥夺的切片培养物中电压依赖性钙通道广泛上调。对活动剥夺切片的钙成像研究表明，自发爆发不是局部行为，而是一种全局同步现象，类似于癫痫活动。这些数据表明，经历稳态重塑的单个神经元的输入/输出转换比简单缩放更为复杂。这种转换的网络后果包括癫痫比例的网络不稳定。自发活动在积极维持网络中的稳态平衡方面起着关键作用，而这种平衡在活动剥夺后会丧失。
