Network properties of starburst amacrine cells during development and in visual processing

Starburst amacrine cells have been implicated in two important network functions, one in spontaneous retinal waves during early visual development and the other in direction selectivity after the onset of vision. In the current study, the interaction between overlapping starburst amacrine cells was investigated across different ages to understand how the same starburst network plays dramatically different functional roles during visual development and visual processing. Using dual patch-clamp recording and Ca2+ uncaging, this study demonstrated Ca2+-dependent corelease of ACh and GABA from single starburst cell in the perinatal rabbit retina. During early retinal development, starburst cells form reciprocal synapses among themselves. The postsynaptic responses at these synapses are mediated by nicotinic and GABA A receptors, which are both excitatory during early development. By forming a network of mutually excitatory neurons, starburst cells play a critical role in mediating spontaneous retinal waves. With maturation, nicotinic synaptic transmission between starburst cells is reduced dramatically to a nearly undetectable level, while the reciprocal GABAergic synapses among starburst cells remain largely intact but change from excitatory to inhibitory. The second part of this study demonstrates that starburst cells form a mutually inhibitory network in the mature retina and that this network provides an inhibitory surround receptive field which is critical for direction selectivity in starburst cell dendrites. The spatial profile of the inhibitory surround was measured under stationary light stimulation, and it was found to match the spatial extent to which two neighboring starburst cells are able to have direct synaptic communication under dual patch recording. Remarkably, when the light stimulus moved centripetally from the surround toward the center of the starburst cell receptive field, there was a GABA-mediated inhibitory input to the starburst cell, which preceded the glutamate-mediated excitatory input to the cell. In contrast, when the light stimulus moved in the centrifugal direction, the glutamate-mediated excitatory current preceded the inhibitory input. These results identified an asymmetric synaptic mechanism for motion detection at the starburst level. This mechanism is based on the combination of a network-driven inhibitory surround with a uniquely asymmetric input-output property of the starburst cell, which transforms a common center-surround receptive field into a motion-detecting unit. In addition to the short range feedforward inhibitory surround GABAA receptors, this study also identified a long range feedback input to bipolar cells mediated by GABAC receptors, which reduces the basal level of glutamate input to starburst cells and causes a net hyperpolarization of starburst cells during the centripetal motion of the light stimulus, suggesting a coordinated inhibitory action by GABA A and GABAC systems during the centripetal image motion. Taken together, this study has revealed age-dependent synaptic properties of starburst cells that allow the network to support retinal waves during development and direction selectivity during retinal processing.