Intercellular Communication in Retinal Development

总结

Summary Neuronal information is immensely enhanced by the diversification of signals at synaptic connections. Postsynaptic cells can display very different outputs despite being connected to the same presynaptic neuron or neuronal cell type. Many pre- and postsynaptic mechanisms can give rise to signal diversification at synapses. In this proposal, we explore the synaptic wiring strategies that can lead to different signal transforms within circuits of known functions. We will determine the synaptic output arrangements of cone bipolar interneurons in the vertebrate retina. Cone bipolar cells are essential for daylight vision, and transfer information to ganglion cells, the output neurons of the retina, at synaptic specializations called dyads. Information may be modified at dyads by a variety of mechanisms, including inhibition from amacrine cells. Preliminary data and previous work show that ganglion cells connected to the same bipolar cell type exhibit very different output properties. Furthermore, ganglion cell types that exhibit distinct outputs receive input from bipolar cells that are morphologically separate but respond similarly to light. Here, we will test the broad hypothesis that there is wiring specificity at synaptic dyads between different types of bipolar cells, amacrine cells and ganglion cells (Aim 1). To do so, we will use a combination of correlative fluorescence imaging and serial block face scanning electron microscopy together with confocal imaging, and transgenic approaches to reconstruct synaptic motifs between specific types of cone bipolar cells and ganglion cells. Because cone bipolar cell dyads are key to synaptic transmission in the retina, we will increase our understanding of how they are assembled properly during development using the same toolset (Aim 2a). Moreover, we still lack a clear understanding of the capacity and constraints of reconnecting neurons appropriately during retinal repair. Using a model of ganglion cell injury and recovery, we will determine how well cone bipolar cell synaptic connections are reassembled when ganglion cells regrow dendrites that had retracted after axotomy (Aim 2b). Together, our studies will significantly advance knowledge of the matrix of synaptic wiring patterns in retinal microcircuits in which visual signals diversify greatly. We will also gain a deeper understanding of how these key synaptic patterns are established during development and potentially regained during circuit regeneration.