David W. Marshak, PhD
ContactDavid W. Marshak, PhD
A Primate Retinal Connectome
The long-term goal of our research is a description of neural circuits in the primate retina at the level of synapses between identified populations of neurons, a retinal connectome. We are now collaborating with the Neitz Laboratory at the University of Washington on a study of the neural circuits that process information from blue cones in the macaque retina. They have imaged serial sections of the central macaque retina using serial block-face scanning electron microscopy, and we are working with them to reconstruct the individual neurons and describe their synapses. We are beginning in the outer plexiform layer, where the rods and cones interact with horizontal cells, inhibitory local circuit neurons. The rods and cones also provide input to bipolar cells, which convey signals to the inner retina, where their targets include retinal ganglion cells, the projection neurons of the retina.
The focus of this study is on the central retina, where midget bipolar cells and their targets, midget ganglion cells, receive input from a single cone. The midget ganglion cells are generally thought to mediate the perception of red and green because they receive excitatory input from a single red or green cone and inhibitory input from the surrounding cones. However, this idea was called into question by a recent psychophysical study. Using adaptive optics, it was possible to simulate a single red or green cone at a time in human subjects. This generally did not give rise to the perception of color; most cones yielded a sensation of white. Only a few cones seemed to generate color sensations. Our working hypothesis is that one type of horizontal cell, called H2, conveys information from the blue cones to a subset of midget bipolar cells that, in turn, provide excitatory input to a subset of midget ganglion cells that give rise to the sensation of color. We have seen synapses in the neuropil of the outer plexiform layer, and we are now reconstructing the pre- and post-synaptic neurons to test this hypothesis. We will also analyze the synaptic output of two types of bipolar cells that selectively contact blue cones. We are particularly interested in their connections with amacrine cells, inhibitory neurons of the inner retina. Our working hypothesis is that these amacrine cells also contribute to the perception of color.
Areas of Interest
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.
- Bordt AS, Perez D, Tseng L, Liu WS, Neitz J, Patterson SS, Famiglietti EV and Marshak DW. Synaptic inputs from identified bipolar and amacrine cells to a sparsely branched ganglion cell in rabbit retina. Visual Neuroscience, 36:E004, 2019. PMID: 31199211.
- Patterson SS, Kuchenbecker JA, Anderson JR, Bordt AS, Marshak DW, Neitz M and Neitz J. An S-cone circuit for edge detection in the primate retina. Scientific Reports 9:11913, 2019. PMID: 31417169
- Patterson SS, Bordt AS, Girresch RJ, Linehan CM, Bauss J, Yeo E, Perez D, Tseng L, Navuluri S, Harris NB, Matthews C, Anderson JR, Kuchenbecker JA, Manookin MB, Ogilvie JM, Neitz J, and Marshak DW. Wide-field amacrine cell inputs to ON parasol ganglion cells in macaque retina. Journal of Comparative Neurology 2019 Dec 17. [Epub ahead of print] PMID: 31845339.