Transformation of visual signals at the synaptic terminals of retinal bipolar cells

For a long time, the retina has been thought to be a part of the brain that performs only simple computations before more complex processes within higher visual centres disentangle the relevant features of the stimulus from the irrelevant background information. However, since the first electrical recordings from retinal ganglion cells in the 1930s, more recent advances in genetic engineering, electrophysiology, and optics, have made it clear that the retina performs intricate feature-extracting computations. Central to these computations is the inner plexiform layer in which the terminals of bipolar cells make connections to the dendrites of ganglion- and amacrine cells. In this thesis, we describe two novel circuits within the inner plexiform layer of larval zebrafish. Chapter 1 comprises a general introduction. Chapter 2 describes the methods we used to study transgenic zebrafish larvae in vivo under two-photon illumination. Chapters 3 and 4 give insights into the computational power of individual bipolar cells. Given that most bipolar cells have multiple output synapses begs the question of whether each synapse can signal different properties of a stimulus. We show that the output synapses of many individual bipolar cells release glutamate in a heterogeneous manner in response to changes in light intensity: some terminals give an excitatory response whenever the light increases (ON) or decreases (OFF), whilst others signal both polarities. This finding contradicts the classical view that ON and OFF pathways are separated from each other before they converge at later stages in the visual system. Chapter 5 comprises an investigation into the emergence of retinal orientation and direction-selectivity. Previous studies have located these properties to the dendritic trees of retinal ganglion cells. However, we show that ~25% of bipolar cell terminals are tuned to the orientation but not the direction of a stimulus. Orientation selectivity could not be explained by asymmetric receptive fields but was removed by blocking inhibition. Chapter 6 encompasses a general discussion.