Volen Center and Biology Department, Brandeis University, Waltham, MA 02454, USA.
Volen Center and Biology Department, Brandeis University, Waltham, MA 02454, USA.
Neuron. 2014 May 21;82(4):809-21. doi: 10.1016/j.neuron.2014.04.002.
How do neurons develop, control, and maintain their electrical signaling properties in spite of ongoing protein turnover and perturbations to activity? From generic assumptions about the molecular biology underlying channel expression, we derive a simple model and show how it encodes an "activity set point" in single neurons. The model generates diverse self-regulating cell types and relates correlations in conductance expression observed in vivo to underlying channel expression rates. Synaptic as well as intrinsic conductances can be regulated to make a self-assembling central pattern generator network; thus, network-level homeostasis can emerge from cell-autonomous regulation rules. Finally, we demonstrate that the outcome of homeostatic regulation depends on the complement of ion channels expressed in cells: in some cases, loss of specific ion channels can be compensated; in others, the homeostatic mechanism itself causes pathological loss of function.
神经元是如何在持续的蛋白质周转和活动干扰的情况下发展、控制和维持其电信号特性的？根据通道表达的分子生物学的一般假设，我们推导出一个简单的模型，并展示它如何在单个神经元中编码“活动设定点”。该模型生成了多种自调节细胞类型，并将体内观察到的电导表达相关性与潜在的通道表达率联系起来。突触和内在电导都可以被调节，以形成一个自组装的中枢模式发生器网络；因此，网络级别的动态平衡可以从细胞自主调节规则中出现。最后，我们证明了动态平衡调节的结果取决于细胞中表达的离子通道的互补性：在某些情况下，特定离子通道的缺失可以得到补偿；在其他情况下，动态平衡机制本身会导致病理性功能丧失。
