Knowledge of how retinal neurons interact is requisite to an understanding of retinal function. Using immunohistochemical techniques, it is now possible to visualize discrete populations of cells and their complex network of processes based on their biochemical signatures. However, only a limited degree of knowledge about nervous system function is gained by placing a biochemically relevant name onto a particular cell or population of cells. The correlation between a cell's biochemical signature and that neuron's particular functions is still largely undefined. This question has become more complicated with the determination that most neurons utilize several neuroactive substances for interneuronal communication. We have found that approximately one half of the synapses made by the glycine-utilizing amacrine cells in the turtle retina are not glycine receptor immunoreactive. It thus appears plausible that neurons utilizing multiple neuroactive substances may maintain appropriate resolution, or segregation of individual neurotransmitter functions by virtue of heterogeneous receptor localization. Therefore, each neuron, and perhaps each synaptic terminal, may be simultaneously involved in several aspects of retinal microcircuitry in order to effect retinal function. In approaching these questions, we will use a combination of intracellular filling and light and electron microscopical immunohistochemistry of pre- synaptic markers (neuroactive substances and their biosynthetic enzymes) as well as the specific receptors involved in post-synaptic responses. The molecular specificity of the receptor antibodies will also be determined by Western blot analysis in the species studied. Using these techniques, we will identify the neuroactive substance and post-synaptic receptor type active at the nonglycinergic synapses made by the glycine-utilizing amacrine cells in the turtle retina. In addition, we elucidate whether similar heterogeneous receptor localization occurs in the rabbit retina. Our focus will be on the glycine-utilizing AII amacrine cell, as well as the cholinergic starburst amacrine cell which may also contain GABA. These studies are designed to increase our understanding of retinal and nervous system function in general, as well as that of particular functional circuits important to the retina in carrying out specific visual functions such as contrast enhancement and motion detection. Such knowledge will ultimately enable us to better understand the consequences of retinal disease.
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