UC Santa Cruz

The retina extracts relevant features from the visual scene and transmits these features to the brain through separate pathways that will eventually result in the perception of sight. The retinal ganglion cells (RGCs) are the only retinal cell type to send an axonal projection to the brain. This indicates that the signals generated by the RGCs are the end result of retinal processing, and the features detected by the RGCs are all that will be transmitted to the brain about the visual environment. Each RGC type represents a unique pathway that detects specific visual features. RGCs of the same type tile the retina so that the entire visual field is sampled. Different types of RGCs overlap so that each pixel in the visual field gets sampled by each pathway. To understand the different retinal pathways and what gets sent to the brain, it is necessary to know what types of RGCs are in the retina. Current classifications have used morphologies and physiology to describe the different RGC types. It is estimated that 20 different types of RGCs are present in the mammalian retina. However, very little is known about how these morphological features affect functional properties due to the inability to perturb the morphology and observe changes in physiology in many mammals. In order to overcome this limitation, I utilized a large-scale multielectrode array (MEA) approach to record and characterize responses from hundreds of RGCs in the mouse retina. The mouse model is advantageous due to the ease of genetic manipulation, allowing me to disrupt morphology and relate the changes to function. I first characterized and classified RGCs in the wild-type retina to develop a reference for mutant comparisons. I was able to classify up to 8 types of RGCs along with functional properties of the classes, such as tiling arrangements of the RGC receptive fields (RFs). Using a mutant mouse that has defects in dendritic and cell body spacing, I show that the dendritic structure is important for RF tiling and direction selective responses thus showing how morphology affects function. Finally, I used a transgenic mouse, in which RGCs expressing a particular gene was ablated, to show that these eliminated RGCs were a distinct functional subset that responded to light offset. The work that I performed will contribute to a complete classification of RGCs by linking the morphological types to the functional types, as well as the genetic programs that establish their properties. This will be necessary to determine what features are detected by the retina and how they ultimately lead to behavior.