Signal processing in horizontal cells of the mammalian retina – coding of visual information by calcium and sodium action potentials

视觉信息是如何在视觉系统的第一个突触中编码的？水平细胞处理由光感受器细胞传递的视觉信息，它们的抑制反馈调节光感受器带突触的囊泡释放。在这里，锥体与水平细胞树突建立化学突触，而杆状细胞与轴突终端系统联系。根据目前的知识，水平细胞是无尖峰的中间神经元，沿连接体细胞和轴突终端系统的轴突传递电紧张信号被认为是不可能的。然而，我们已经在水平细胞的细胞体和树突中观察到基于钙的动作电位，以及局限于轴突末端系统的钠介导电流。这些结果表明，梯度电位和动作电位对不同水平细胞区室的视觉信号处理都有影响。梯度电位和动作电位之间的动态变化对应着从模拟信号到数字信号的转变。这种开关影响着细胞内信号的空间分布和时间结构，因此对视觉信息的编码具有极其重要的意义。动作电位的产生将重点从局部树突信号处理转移到整个细胞作为一个整体结构。关于水平细胞通过间隙连接的功能耦合，整合过程甚至可能包括单个神经元的大网络，从而包括视网膜的大量区域。此外，动作电位的产生是细胞体和轴突末端之间电通信的先决条件。这两个隔室之间的相互信号交换可能使视觉系统的第二神经元水平上的暗位和光位信息流的迄今未知的相互作用成为可能。在目前的应用中，我们将确定水平细胞表达的电压门控钠和钙通道的亚型，以及它们的亚细胞分布和频率。利用膜片钳技术，我们将以高时间分辨率记录动作电位，并确定其编码视觉刺激的精度。这些实验将适合于确定决定从分级信号到动作电位转换的参数。钙介导信号的空间分布将通过高频成像技术解决。该实验旨在深入了解视觉信息在感觉加工的早期阶段的时空编码。编码视觉信息的动作电位扩展了单个突触的功能范围，从而从根本上影响了反馈机制的全细胞整合和下游神经元感受野结构的动态。

How is visual information encoded at the first synapse of the visual system? Horizontal cells process visual information transmitted by photoreceptor cells, and their inhibitory feedback modulates vesicle release at the photoreceptor ribbon synapse. Here, cones establish chemical synapses with horizontal cell dendrites, whereas rods contact the axon terminal system. According to current knowledge, horizontal cells are non-spiking interneurons, and electrotonic signal transfer along the axon connecting the soma and the axon terminal system is considered impossible.However, we have observed calcium-based action potentials in cell bodies and dendrites of horizontal cells as well as sodium-mediated currents confined to the axon terminal system. These findings suggest that both graded potentials and action potentials contribute to visual signal processing in different horizontal cell compartments. The dynamic change between graded potentials and action potentials corresponds to a transition from analog to digital signaling. This switch influences the spatial distribution and temporal structure of intracellular signals, and it is therefore of extreme importance for the coding of visual information. The generation of action potentials shifts emphasis from local dendritic signal processing to the entire cell as an integrative structure. Concerning the functional coupling of horizontal cells via gap junctions, the integration process might even encompass a large network of individual neurons and thus a substantial area of the retina.Furthermore, the generation of action potentials is a prerequisite for electrical communi-cation between the cell body and the axon terminal. The mutual exchange of signals be-tween the two compartments would make possible a so far unknown interaction of scotopic and photopic information flow at the level of the second neuron of the visual system.In the present application, we will identify subtypes of voltage-gated sodium and calcium channels expressed by horizontal cells, as well as their subcellular distribution and frequency. Using the patch-clamp technique, we will record action potentials with high temporal resolution and determine the precision of their encoding of visual stimuli. These experiments will be suited to identify parameters determining the switch from graded signaling to action potentials. The spatial distribution of calcium-mediated signals will be resolved with high-frequency imaging techniques.The experiments are designed to gain profound insight into the spatio-temporal coding of visual information at a very early stage of sensory processing. Action potentials encoding visual information expand the functional scope of individual synapses, and therefore they influence the cell-wide integration of feedback mechanisms and the dynamics of receptive field structures of downstream neurons in fundamental ways.