Human and macaque monkey eyes have red, green, and blue cones. Their synaptic terminals contact horizontal cells and cone bipolar cells of approximately 9 types, two midget (one ON and one OFF), a distinctive blue ON, and six diffuse (ON and OFF). These parallel bipolar pathways are ultimately responsible for the receptive field structures of many types of ganglion cell, which provide the signals that are processed by visual cortex. The special focus of this proposal is on the systems of synapses that drive each type of retinal cell. After five years of collaborative work on 2000x electron micrographs that blanket 319 serial sections of a small region of the central retina of macaque monkey, every cell and terminal in the series can be identified. The three cone types can be distinguished by features of the bipolar cells that they contact; however, these features do not identify which is red and which is green. It is known for human retina that red cones outnumber green, so red midget bipolar cells will be identified as the one in the majority in the human retina. With higher magnification micrographs (5000x and 10000x) blanketing the synaptic layers in our series of sections, it will be possible to exhaustively account for all the synaptic contacts of reconstructed cells and to analyze whole systems of synapses. Here are some questions that this approach will allow us to answer: Cones make approximately 100 synaptic contacts of several types. How many and what type contact each bipolar and horizontal cell? How are these systems organized with respect to each other and with respect to special morphological features of the cone's synaptic terminal? Is it possible that each (ribbon) site that releases neurotransmitter services many more synaptic targets than is currently believed? How do synaptic systems of contacts vary among the three types of cone circuits? Finally, do these findings support current classification schemes for bipolar and horizontal cells? Central retina, containing the fovea or macula, is the region of finest acuity and color vision. It is the most critical part of the retina, as reflected by the prevalence and seriousness of macular degeneration, and it dominates visual function. Better understanding of retinal function, particularly macular function, will facilitate diagnosis, discrimination, and treatment of retinal visual disorders, and give insight into visual cortical function and dysfunction as well.
