Lipin Mikhail Y, Vigh Jozsef
Department of Biomedical Sciences, Colorado State University, Fort Collins, Colorado.
Department of Biomedical Sciences, Colorado State University, Fort Collins, Colorado
J Neurophysiol. 2015 Jan 15;113(2):550-66. doi: 10.1152/jn.00378.2014. Epub 2014 Oct 22.
Most retinal bipolar cells (BCs) transmit visual input from photoreceptors to ganglion cells using graded potentials, but some also generate calcium or sodium spikes. Sodium spikes are thought to increase temporal precision of light-evoked BC signaling; however, the role of calcium spikes in BCs is not fully understood. Here we studied how calcium spikes and graded responses mediate neurotransmitter release from Mb-type BCs, known to produce both. In dark-adapted goldfish retinal slices, light induced spikes in 40% of the axon terminals of intact Mbs; in the rest, light generated graded responses. These light-evoked membrane potentials were used to depolarize axotomized Mb terminals where depolarization-evoked calcium current (ICa) and consequent exocytosis-associated membrane capacitance increases (ΔCm) could be precisely measured. When evoked by identical dim light intensities, spiking responses transferred more calcium (Q(Ca)) and triggered larger exocytosis with higher efficiency (ΔCm/Q(Ca)) than graded potentials. Q(Ca) was translated into exocytosis linearly when transferred with spikes and supralinearly when transferred with graded responses. At the Mb output (ΔCm), spiking responses coded light intensity with numbers and amplitude whereas graded responses coded with amplitude, duration, and steepness. Importantly, spiking responses saturated exocytosis within scotopic range but graded potentials did not. We propose that calcium spikes in Mbs increase signal input-output ratio by boosting Mb glutamate release at threshold intensities. Therefore, spiking Mb responses are suitable to transfer low-light-intensity signals to ganglion cells with higher gain, whereas graded potentials signal for light over a wider range of intensities at the Mb output.
大多数视网膜双极细胞（BCs）利用分级电位将光感受器的视觉输入传递给神经节细胞，但也有一些双极细胞会产生钙峰或钠峰。钠峰被认为可提高光诱发的双极细胞信号传导的时间精度；然而，双极细胞中钙峰的作用尚未完全明确。在此，我们研究了钙峰和分级反应如何介导Mb型双极细胞（已知能产生这两者）的神经递质释放。在暗适应的金鱼视网膜切片中，光照可使完整Mb细胞40%的轴突终末产生峰电位；其余的则产生分级反应。这些光诱发的膜电位被用于使切断轴突的Mb终末去极化，在此处可以精确测量去极化诱发的钙电流（ICa）以及随之而来的与胞吐作用相关的膜电容增加（ΔCm）。当由相同的暗光强度诱发时，与分级电位相比，峰电位反应传递了更多的钙（Q(Ca)），并以更高的效率触发了更大的胞吐作用（ΔCm/Q(Ca)）。当通过峰电位传递时，Q(Ca)与胞吐作用呈线性关系，而通过分级反应传递时则呈超线性关系。在Mb输出端（ΔCm），峰电位反应通过数量和幅度编码光强度，而分级反应则通过幅度、持续时间和陡度进行编码。重要的是，峰电位反应在暗视范围内使胞吐作用达到饱和，而分级电位则不会。我们提出，Mb细胞中的钙峰通过在阈值强度下增强Mb谷氨酸释放来提高信号输入输出比。因此，产生峰电位的Mb反应适合以更高的增益将低光强度信号传递给神经节细胞，而分级电位则在Mb输出端对更广泛强度范围内的光进行信号编码。
