GLEASON, Evanna L.; Louisiana State University: Signaling and modulation in retinal amacrine cells

Signal processing in the vertebrate retina depends upon the transfer of information between retinal neurons at their synapses. Amacrine cells are a morphologically and functionally diverse group of retinal interneurons that signal primarily in the inner retina. Although amacrine cells make up a substantial fraction of retinal neurons, they have proven difficult to study, and we know the least about them. To study the regulation of intra- and intercellular signaling in amacrine cells, we employ a culture system consisting of retinal neurons derived from the chick embryo. In these cultures, identifiable amacrine cells mature and form functional GABAergic synapses with one another. Although we have investigated the roles of several potential modulators, here I will focus on glutamate. In the retina, glutamate from bipolar cells excites amacrine cells by binding to ionotropic glutamate receptors. Additionally, glutamate has the potential to engender more complex responses in amacrine cells through the binding of g-protein coupled, metabotropic glutamate receptors (mGluRs). Immunocytochemistry in the chicken retina indicated that amacrine cells express mGluR5. Calcium imaging experiments on cultured amacrine cells have shown that activation of this receptor stimulates the IP₃ pathway and leads to cytosolic calcium elevations. To begin to understand the synaptic targets of this modulatory pathway, we have examined the effects of mGluR5 activation on currents through voltage-gated Ca²⁺ channels and GABA_A receptors. Activation of mGluR5 leads to an enhancement of both voltage-gated Ca²⁺ currents and GABA-gated currents, however, the underlying mechanisms are distinctive. In the retina, this mGluR5-dependent enhancement of amacrine cell signaling could strengthen GABAergic feedback to bipolar cells as well as strengthen GABAergic signaling between amacrine cells.