David W. Marshak, PhD

Professor
Neurobiology & Anatomy
McGovern Medical School
UTHealth Houston

Email:     David.W.Marshak@uth.tmc.edu
Phone:   713-500-5617

Biography

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 macaque retina. They have imaged serial sections of central macaque retina using serial blockface 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 stimulate 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 the 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.

Educational Philosophy

I have been very fortunate to spend my entire career teaching graduate and professional students, all very bright and highly motivated to learn. Most of my efforts have gone toward teaching first year medical students about human anatomy, a topic that they find difficult, but rewarding, to learn. In the new curriculum, my lectures are now short videos online, and I do my teaching in person in the anatomy laboratory. I have also promoted active learning by posting quizzes, consisting of 40-50 fill-in-the-blank questions per lecture, on Canvas. I give a traditional lecture on the development of the gastrointestinal system, but it is augmented with videos.
In my research laboratory, we have a very diverse group with training in a wide variety of disciplines, and we collaborate frequently with other investigators using approaches entirely different than ours. I have been able to achieve my teaching goals in Vision I, where I do not lecture at all. Instead, teams of graduate students make presentations on the topic based on recent scientific papers. I also participate in the Vision Journal Club.

I have trained two Ph.D. students in my laboratory, and they have both been very successful. The first, Roy Jacoby, is now an assistant professor at Baylor College of Medicine, and the second, Matt Gastinger, is a support manager at Bitplane Scientific Software. An M.S. student, Alejandro Vila, went on to get a Ph.D. and now represents Olympus in Southern California. I have also mentored some outstanding postdoctoral fellows at UT Houston. Elizabeth Yamada, Yongchun Yu and Nobuo Kouyama are now associate professors. Sally Firth, Hideo Hoshi, Renata Frazao and Hiromasa Satoh are assistant professors. Ye Long is a researcher at Baylor College of Medicine, Garrett Kenyon is a staff scientist at Los Alamos National Laboratory, Nicolai Larsen is a physician-scientist, and Donna Stafford is an academic administrator.

Areas of Interest

Neuroanatomy
Electron Microscopy
Imunohistochemistry

Publications

Visit the PubMed profile page

  • Bordt AS, Patterson SS, Girresch RJ, Perez D, Tseng L, Anderson JR, Mazzaferri MA, Kuchenbecker JA, Gonzales-Rojas R, Roland A, Tang C, Puller C, Chuang AZ, Ogilvie JM, Neitz J and Marshak DW. Synaptic inputs to broad thorny ganglion cells in macaque retina.  Journal of Comparative Neurology Aug 1;529(11):3098-311, 2021 PMID: 33843050
  • Bordt AS, Patterson SS, Kuchenbecker JA, Mazzaferri MA, Yearick JN, Yang ER, Ogilvie JM, Neitz J, Marshak DW. Synaptic inputs to displaced intrinsically-photosensitive ganglion cells in macaque retina. Scientific Reports 12(1):15160, 2022 PMID: 36071126
  • Goyal M, Bordt AS, Neitz J, Marshak DW. Trogocytosis of neurons and glial cells by microglia in a healthy adult macaque retina. Scientific Reports 13(1):633, 2023 PMID: 36635325
  • Patterson SS, Girresch RJ, Mazzaferri MA, Bordt AS, Piñon-Teal WL, Jesse BD, Perera DW, Schlepphorst MA, Kuchenbecker JA, Chuang AZ, Neitz J, Marshak DW, Ogilvie JM. Synaptic Origins of the Complex Receptive Field Structure in Primate Smooth Monostratified Retinal Ganglion Cells. eNeuro. 2024 Jan 30;11(1). PMID: 38290840