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

在视觉系统的第一个突触，视觉信息是如何编码的？水平细胞处理光感受器细胞传递的视觉信息，它们的抑制性反馈调节光感受器带状突触的囊泡释放。在这里，锥体与水平细胞树突建立化学突触，而杆接触轴突终末系统。根据现有的知识，水平细胞是非尖峰中间神经元，电渗性信号沿连接胞体和轴突终末系统的轴突传递被认为是不可能的。然而，我们在水平细胞的细胞体和树突中观察到基于钙的动作电位，以及仅限于轴突终末系统的钠介导的电流。这些发现表明，分级电位和动作电位都参与了不同水平细胞间的视觉信号加工。分级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过渡。这种转换影响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非常重要。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完整的结构。至于水平细胞通过缝隙连接的功能耦合，整合过程甚至可能包括一个由单个神经元组成的大网络，从而可能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终末之间进行电交流的先决条件。这两个隔室之间的相互信号交换将使视觉系统第二神经元水平上的暗视和明视信息流之间的未知相互作用成为可能。在本应用中，我们将识别水平细胞表达的电压门控钠通道和钙通道的亚型，以及它们的亚细胞分布和频率。利用膜片钳技术，我们将记录高时间分辨率的动作电位，并确定其对视觉刺激的编码精度。这些实验将适合于识别决定从分级信号到动作电位的切换的参数。钙离子介导的信号的空间分布将通过高频成像技术来解决。实验旨在深入了解视觉信息在感觉加工的非常早期阶段的时空编码。编码视觉信息的动作电位扩大了单个突触的功能范围，因此它们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场结构的动力学。

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.