Intercellular Communication in Retinal Development

视网膜回路对光信息的处理关键取决于两者的相互作用

The processing of light information by retinal circuits depends critically on the interplay between excitatory and inhibitory neurotransmission. The output of retinal ganglion cells (RGCs) to higher visual centers is shaped by a balance of excitation and inhibition provided by their presynaptic partners, bipolar cells and amacrine cells. Direct inhibition onto RGCs and feedback inhibition onto presynaptic bipolar cells contribute to the final output profile of the RGCs. Previously, we examined how excitatory synapses are established at appropriate densities across the dendritic arbor of RGCs during development and discovered that perturbation of excitatory transmission from bipolar cells results in a reduction in glutamatergic synapses on RGC dendrites. Here, we propose to test the hypothesis that neurotransmission during development regulates the development of inhibitory inputs onto RGCs, and coordinates the maturation of the balance of excitation and inhibition onto these cells. We will also test the hypothesis that transmission influences the development of feedback inhibition onto the axon terminals of the bipolar cells. In Aim 1, we will determine the mature organization of inhibitory synapses onto RGC dendrites and examine how these patterns arise during development. This will be achieved using confocal and multiphoton imaging of RGCs with fluorescently tagged inhibitory postsynaptic sites. These experiments are needed to reveal the spatial and temporal relationships of the development of inhibitory and excitatory synapses on the dendrites of individual RGCs. In Aim 2, we will directly test the hypothesis that neurotransmission regulates inhibitory synapse development on RGCs using transgenic mice in which either glutamatergic or GABAergic transmission is markedly suppressed. In Aim 3, we will determine how feedback inhibition onto rod bipolar cells develop and ascertain the role of neurotransmission in the assembly of this synapse using the transmission-perturbed mice. Taken together, the results from these aims will advance our knowledge of how inhibitory circuits in the inner retina develop, and help define the role(s) of neurotransmission in attaining the proper wiring of retinal circuits or their miswiring in injury and disease.