Cell communication mechanisms in the vertebrate retina: The Proctor Lecture

The vertebrate retina has a unique position within the panoply of the nervous system networks: Our understanding of its complex circuitry of interacting neurons and glia has become the gold standard of our current knowledge of network operations. This presentation is about work from my laboratory that contributed to some of the concepts that support our contemporary views of the functional retina. Early in the pursuit of retinal function, a vital issue was that of understanding the synaptic mechanisms and neurotransmitters required for information to flow from the photoreceptors to the ganglion cells. My research contributions to this effort include the discovery of inhibition and the GABA and glycine modes of inhibitory mechanisms. Our work on inhibition was followed by the discovery of the APB (mGluR6) receptor of On bipolars, the first metabotropic glutamate receptor described in the nervous system. This finding was followed by a body of work carried out in salamander and rabbit retinas on the pathways of glutamatergic excitation revealed through the use of agonists and antagonists of increasing selectivity. We separated sign-conserving from sign-inverting responses in the outer retina and provided compelling evidence that bipolars, like photoreceptors, had a glutamatergic mode of neurotransmission. We identified NMDA (N-methyl-D- aspartate) and KA (kainic acid)/AMPA (α-amino-3-hydroxy-5-methyl-4- isoxazolepropionic acid) receptors in amacrine and ganglion cells and revealed that both receptor classes are activated by light. Additional studies on neuropeptides illustrated how many of these, including substance P, somatostatin, and neurotensin have actions such that they should be considered major neuromodulators in the retina. My laboratory also made significant contributions to structure-function relationships and mechanisms of glial-neuronal interactions.