Kameneva Tatiana, Meffin Hamish, Burkitt Anthony N
Department of Electrical Engineering, The University of Melbourne, Bld. 193 room 4.2, VIC 3010, Australia.
J Comput Neurosci. 2011 Nov;31(3):547-61. doi: 10.1007/s10827-011-0322-3. Epub 2011 Mar 23.
ON and OFF retinal ganglion cells (RGCs) display differences in their intrinsic electrophysiology: OFF cells maintain spontaneous activity in the absence of any input, exhibit subthreshold membrane potential oscillations, rebound excitation and burst firing; ON cells require excitatory input to drive their activity and display none of the aforementioned phenomena. The goal of this study was to identify and characterize ionic currents that explain these intrinsic electrophysiological differences between ON and OFF RGCs. A mathematical model of the electrophysiological properties of ON and OFF RGCs was constructed and validated using published patch-clamp data from isolated intact mouse retina. The model incorporates three ionic currents hypothesized to play a role in generating behaviors that are different between ON and OFF RGCs. These currents are persistent Na( + ), I (NaP), hyperpolarization-activated, I (h), and low voltage activated Ca(2 + ), I (T), currents. Using computer simulations of Hodgkin-Huxley type neuron with a single compartment model we found two distinct sets of I (NaP), I (h), I (T) conductances that correspond to ON and OFF RGCs populations. Simulations indicated that special properties of I (T) explain the differences in intrinsic electrophysiology between ON and OFF RGCs examined here. The modelling shows that the maximum conductance of I (T) is higher in OFF than in ON cells, in agreement with recent experimental data.
视网膜上的ON型和OFF型神经节细胞(RGCs)在其内在电生理特性上存在差异:OFF型细胞在没有任何输入的情况下保持自发活动,表现出阈下膜电位振荡、反弹兴奋和爆发式放电;ON型细胞需要兴奋性输入来驱动其活动,并且不表现出上述任何现象。本研究的目的是识别和表征能够解释ON型和OFF型RGCs之间这些内在电生理差异的离子电流。利用从分离的完整小鼠视网膜中获得的已发表的膜片钳数据,构建并验证了ON型和OFF型RGCs电生理特性的数学模型。该模型纳入了三种假设在产生ON型和OFF型RGCs之间不同行为中起作用的离子电流。这些电流分别是持续性钠电流(I(NaP))、超极化激活电流(I(h))和低电压激活钙电流(I(T))。使用单室模型的霍奇金-赫胥黎型神经元的计算机模拟,我们发现了两组不同的I(NaP)、I(h)、I(T)电导,它们分别对应于ON型和OFF型RGCs群体。模拟表明,I(T)的特殊性质解释了此处研究的ON型和OFF型RGCs之间内在电生理的差异。建模显示,OFF型细胞中I(T)的最大电导高于ON型细胞,这与最近的实验数据一致。