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

• Applicant: Professor Dr. Andreas Feigenspan
• Subject Area: Molecular Biology and Physiology of Neurons and Glial Cells
• Term: from 2019 to 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 422915148

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.

• DFG Programme: Research Grants