The long-term goal of our research is a description of neural circuits in the primate retina at the level of synapses between specific types of neurons. This will be an important step toward understanding the first stages in human vision and also information processing in the central nervous system, generally. There has been considerable progress in identifying the subtypes of each major type of retinal neuron. The synaptic interactions in the outer retina have also been described, as have many of the excitatory synapses in the inner retina. Amacrine cells, inhibitory local circuit neurons of the inner retina, are clearly important for information processing in primate retina, because their synapses are the most common type in the inner plexiform layer. However, the synaptic connections of most types of amacrine cells are still not well-understood.
We are now using anatomical and physiological techniques to study amacrine cells that use the neurotransmitter glycine. There are several morphological types, and, together, they comprise half the amacrine cells in primates. Nearly all of the work to date has been on only one type of glycinergic amacrine cell, the AII cell. Based on work with other types of retinal neurons, however, it is likely that there will be important differences between the glycinergic amacrine cell types. We are now describing two other glycinergic amacrine cells that can be selectively labeled with antibodies, a bistratified type and knotty type 2. The focus will be on their contributions to the neural circuits that provide input to two major types of retinal ganglion cells in primates, parasol cells and midget cells. We predict that the bistratified cells are presynaptic to parasol cells and interact with the amacrine cells and diffuse bipolar cells that provide their input. We also predict that knotty 2 cells are presynaptic to AII cells, OFF midget bipolar cells and OFF midget ganglion cells.
In some experiments, one type of cell is labeled by immunohistochemistry and studied by electron microscopy. In others, two cells are labeled using similar techniques or else intracellular injection, the tissue is labeled with a synaptic marker, and the triple labeled material is analyzed by confocal microscopy. The two approaches are complementary. Electron microscopy allows for greater confidence in identifying synapses, and some types of neurons can be identified by their characteristic ultrastructure. However, electron microscopic double labeling is difficult, and undersampling is a very common problem. These limitations are addressed by the light microscopic experiments. Our collaborator, Dr. Roy Jacoby, uses a macaque retinal slice preparation to determine whether these amacrine cells receive excitatory input from ON bipolar cells.
|Amacrine cells containing vGluT3 (black) are expected to interact with both types of cholinergic amacrine cells (blue) and to receive excitatory input from both ON (5) and OFF (7) bipolar cells (green) . They are also expected to provide inhibitory input to both ON and OFF parasol cells (6, 8).||Knotty 2 amacrine cells (black) are expected to be presynaptic to (1) OFF midget bipolar cells (green), (3) OFF midget ganglion cells (red) and (4) AII amacrine cells in the distal half of the IPL. They are also expected to receive input from (5) ON bipolar cells (green) and, possibly, ( 2) OFF midget bipolar cells.|
Yu, Y.C., Satoh, H., Wu, S.M. and Marshak, D.W. Histamine enhances voltage-gated potassium currents of ON bipolar cells in macaque retina. Investigative Ophthalmology and Visual Science 50, 959-965, 2009.
Klump, K. E., Zhang, A.-J. , Wu, S. M., and Marshak, D.W. Parvalbumin-immunoreactive amacrine cells of macaque retina. Visual Neuroscience 26, 287-296, 2009.
Field, G.D., Greschner, M., Gauthier, J.L., Rangel, C., Shlens, J., Sher, A., Marshak, D.W., Litke, A.M. and Chichilnisky, E.J. High sensitivity rod photoreceptor input to the blue-yellow color opponent pathway in macaque retina. Nature Neuroscience 12: 1159-64, 2009.
Akimov, N., Marshak, D.W., Frishman, L.J., Glickman R.D. and Yusupov R.G. Histamine reduces flash sensitivity of ON retinal ganglion cells in primate retina. Investigative Ophthalmology and Visual Science, 51: 3825-3834, 2010.
Yu, Y, Satoh, H. , Vila, A., Wu, S.M., and Marshak, D.W. Effects of histamine on light responses of amacrine cells in tiger salamander retina. Neurochemical Research, 36, 645-654, 2011.
Frazão, R., McMahon, D.G., Schunack, W., Datta, P., Heidelberger, R. and Marshak, D.W. Histamine elevates free intracellular calcium in mouse retinal dopaminergic cells via H1-receptors. Investigative Ophthalmology and Visual Science, 52, 3083-3088, 2011.
Logan J.M., Thompson, A.J. and Marshak, D.W. Testing to enhance retention in human anatomy. Anatomical Sciences Education, 5,243-248, 2011.
Vila, A., Satoh, H., Rangel, C., Mills, S.L., Hoshi, H., O’Brien, J., Marshak, D.R., MacLeish, P.R. and Marshak, D.W. Histamine receptors of cones and horizontal cells in Old World monkey retinas. Journal of Comparative Neurology, 520, 528-543, 2012.
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