Retinal ganglion cells (RGCs) are the neuronal connections between the eye and the brain conveying multiple features of the outside world through parallel pathways. While there is a large body of literature how these pathways arise in the retinal network, the process of converting presynaptic inputs into RGC spiking output is little understood. In this study, we show substantial differences in the spike generator across three types of alpha RGCs in female and male mice, the αON sustained, αOFF sustained and αOFF transient RGC. The differences in their intrinsic spiking responses match the differences of the light responses across RGC types. While sustained RGC types have spike generators that are able to generate sustained trains of action potentials at high rates, the transient RGC type fired shortest action potentials enabling it to fire high-frequency transient bursts. The observed differences were also present in late-stage photoreceptor-degenerated retina demonstrating long-term functional stability of RGC responses even when presynaptic circuitry is deteriorated for long periods of time. Our results demonstrate that intrinsic cell properties support the presynaptic retinal computation and are, once established, independent of them.Significance Statement Spiking output from retinal ganglion cells (RGCs) has long been thought to be solely determined by synaptic inputs from the retinal network. We show that the cell-intrinsic spike generator varies across RGC populations and therefore that postsynaptic processing shapes retinal spiking output in three types of mouse alpha RGCs (αRGCs). While sustained αRGC types have spike generators that are able to generate sustained trains of action potentials at high rates, the transient αRGC type fired shortest action potentials enabling them to fire high-frequency transient bursts. Computational modeling suggests that intrinsic response differences are not driven by dendritic morphology but by somatodendritc biophysics. After photoreceptor degeneration, the observed variability is preserved indicating stable physiology across the three αRGC types.

中文翻译：

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持续和瞬时小鼠 α RGC 中的差异内在放电特性与它们的光响应特性相匹配，并在视网膜变性期间持续存在。


视网膜神经节细胞 （RGC） 是眼睛和大脑之间的神经元连接，通过平行途径传递外界的多种特征。虽然有大量文献说明这些通路如何在视网膜网络中产生，但将突触前输入转换为 RGC 尖峰输出的过程知之甚少。在这项研究中，我们显示了雌性和雄性小鼠中三种类型的 α RGC 的尖峰发生器存在显着差异，即 αON 持续、αOFF 持续和 αOFF 瞬时 RGC。它们固有尖峰响应的差异与 RGC 类型之间光响应的差异相匹配。虽然持续 RGC 类型具有能够以高速率产生持续动作电位序列的尖峰发生器，但瞬态 RGC 类型发射最短的动作电位，使其能够发射高频瞬态爆发。观察到的差异也存在于晚期光感受器退化的视网膜中，表明即使突触前回路长时间恶化，RGC 反应也具有长期功能稳定性。我们的结果表明，内在细胞特性支持突触前视网膜计算，并且一旦建立，就独立于它们。意义声明 长期以来，人们一直认为视网膜神经节细胞 （RGC） 的脉冲输出完全由视网膜网络的突触输入决定。我们表明细胞内在的尖峰发生器因 RGC 群体而异，因此突触后加工塑造了三种类型的小鼠 alpha RGC （αRGC） 的视网膜尖峰输出。 虽然持续 αRGC 类型具有能够以高速率产生持续动作电位序列的尖峰发生器，但瞬态 αRGC 类型发射最短的动作电位，使它们能够发射高频瞬态爆发。计算模型表明，内在响应差异不是由树突形态驱动的，而是由体茎生物物理学驱动的。光感受器变性后，观察到的变异性得以保留，表明三种 αRGC 类型的生理机能稳定。