The idea that the nervous system maintains a set point of network activity and homeostatically returns to that set point in the face of dramatic disruption—during development, after injury, in pathologic states, and during sleep/wake cycles—is rapidly becoming accepted as a key plasticity behavior, placing it alongside long-term potentiation and depression. The dramatic growth in studies of homeostatic synaptic plasticity of miniature excitatory synaptic currents (mEPSCs) is attributable, in part, to the simple yet elegant mechanism of uniform multiplicative scaling proposed by Turrigiano and colleagues: that neurons sense their own activity and globally multiply the strength of every synapse by a single factor to return activity to the set point without altering established differences in synaptic weights. We have recently shown that for mEPSCs recorded from control and activity-blocked cultures of mouse cortical neurons, the synaptic scaling factor is not uniform but is close to 1 for the smallest mEPSC amplitudes and progressively increases as mEPSC amplitudes increase, which we term divergent scaling. Using insights gained from simulating uniform multiplicative scaling, we review evidence from published studies and conclude that divergent synaptic scaling is the norm rather than the exception. This conclusion has implications for hypotheses about the molecular mechanisms underlying synaptic scaling.

神经系统维持网络活动的设定点，并在面对剧烈破坏时（在发育期间、受伤后、病理状态下以及睡眠/觉醒周期期间）稳态地恢复到该设定点的观点正在迅速被接受为关键的可塑性行为，将其与长期增强和抑制并列。微型兴奋性突触电流（mEPSC）的稳态突触可塑性研究的急剧增长部分归因于 Turrigiano 及其同事提出的简单而优雅的均匀乘法缩放机制：神经元感知自己的活动并全局倍增强度每个突触通过一个因素将活动恢复到设定点，而不改变突触权重的既定差异。我们最近表明，对于从小鼠皮质神经元的对照和活动阻断培养物中记录的 mEPSC，突触缩放因子并不均匀，但对于最小的 mEPSC 振幅接近 1，并且随着 mEPSC 振幅的增加而逐渐增加，我们将其称为发散缩放。利用从模拟均匀乘法缩放中获得的见解，我们回顾了已发表研究的证据，并得出结论：发散的突触缩放是常态而不是例外。这一结论对关于突触缩放的分子机制的假设具有影响。