Relating structure to function: Development of dendritic arborisations underlying orientation selectivity in the vertebrate visual system

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Structure and function in the nervous system are closely related, but it is not clear how structure-function relationships develop. One example where the structural diversity of cells is clearly evident is the vertebrate retina. It consists of over 70 different types of neurons with the function to transform light information into electrochemical signals and send them to the brain. Interestingly, visual information is pre-processed already in the retina and split into different channels, such as motion, colour or edges. This is done through the formation of distinct networks between different retinal cells, for example amacrine cells and retinal ganglion cells. Amacrine cells are the most diverse (and least studied) class of neurons in the retina, with many distinct shapes. Although some progress has been made in uncovering factors that influence shape, complexity and connectivity of neurons, our knowledge about the exact mechanisms is limited and many processes are still unclear. This project will use two specific types of amacrine cells in the retina -previously identified by us- that have a striking correspondence between morphology and function as a model to study how such neuronal structure-function relationships in the brain are generated. These cells form many processes or arbours (called dendrites) that are in the shape of elongated structures, similar to elliptic areas. We found that these ellipses are arranged radially in the eye, meaning along the axis from the middle of the retina to the outside. Our results demonstrated that these cells are crucial for detection of oriented visual stimuli, a key element in visual information. However, it is not clear a) what are the developmental steps to form these elliptic cellular structures, b) what influences the generation of this cellular shape and c) how this shape is related to their connected cells in the retina. Using the zebrafish model system, we will follow the structural development of these specific amacrine cells and identify the individual steps until they are functionally mature. To do so, we will use genetic tools already available in our laboratory to label these cells specifically and image them in live animals under the microscope. In a second set of experiments, we will investigate how different parameters will influence the development of our amacrine cells. For this we will alter activity in these neurons (for example keep the fish in the dark to abolish visual input), change the expression of certain genes in them or alter the cellular composition of the retina and then follow the structural development as before. This will answer some important questions about the mechanisms to control cellular structure. Finally, to identify which other cells connect to these specific amacrine cells and map their points of contact (synapses), we will use a state-of-the-art technology based on electron microscopy to create very detailed 3D models of the cellular structures in the retina. This will allow us to identify how the particular amacrine structure is arranged in relation to the structure of other cells and thus the underlying mechanisms for their specific function. Our work will be an important step forward towards better understanding how structure-function relationships develop in the nervous system.