Modelling intrinsic electrophysiological properties of ON and OFF retinal ganglion cells
Modelling intrinsic electrophysiological properties of ON and OFF retinal ganglion cells
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DOI：
10.1007/s10827-011-0322-3
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发表时间：
2011-11-01
影响因子：
1.2
通讯作者：
Burkitt, Anthony N.
中科院分区：
文献类型：
--
作者：
Kameneva, Tatiana;Meffin, Hamish;Burkitt, Anthony N.
ON 和 OFF 视网膜神经节细胞 (RGC) 在其内在电生理学方面表现出差异：OFF 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、反弹兴奋和爆发放电； ON 细胞需要兴奋性输入来驱动其活动，并且不会表现出上述任何现象。本研究的目的是识别和表征离子电流，以解释 ON 和 OFF RGC 之间的这些内在电生理差异。使用已发表的来自分离的完整小鼠视网膜的膜片钳数据构建并验证了 ON 和 OFF RGC 的电生理特性的数学模型。该模型包含三种离子电流，假设它们在产生开和关 RGC 之间不同的行为方面发挥作用。这些电流是持续的 Na (+) 、I (NaP) 、超极化激活的 I (h) 和低电压激活的 Ca2+ 、I (T) 电流。使用单室模型对 Hodgkin-Huxley 型神经元进行计算机模拟，我们发现了两组不同的 I (NaP)、I (h)、I (T) 电导，分别对应于 ON 和 OFF RGC 群体。模拟表明 I (T) 的特殊性质解释了此处检查的 ON 和 OFF RGC 之间内在电生理学的差异。模型显示，OFF 细胞中 I (T) 的最大电导高于 ON 细胞，这与最近的实验数据一致。
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 Ca2 + , 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.