Our visual system perceives the world as functions of time, space, and color. The time (temporal) information, defining the speed of an object ranging from fast moving to stationary, is encoded in temporal processing pathways in the visual system. These pathways are broadly classified into transient pathways and sustained pathways based on their neural responses. The former encodes fast changing visual information, whereas the latter encodes static information. Earlier work suggested that these different temporal processing pathways occurred in retinal ganglion cells. Two morphologically different ganglion cells (a- and ?-ganglion cells) were the origin for these two distinct functional pathways. Recent studies have suggested that retinal bipolar cells, which are upstream of ganglion cells, are critical for the parallel processing of visual information. Morphological studies have revealed more than 10 subtypes of bipolar cells in the mammalian retina, which might initiate distinct pathways encoding different features of temporal signals. To date, no studies have addressed how each subtype of bipolar cell in the mammalian retina encodes temporal visual information. In response to this research gap, my goal is to understand the cellular and molecular mechanisms of temporal encoding in each subtype of ON bipolar cell. In the proposed study, I will investigate how each subtype of ON bipolar cell encodes distinct temporal visual information in the mammalian retina. First, I will examine physiological aspects of temporal encoding in each subtype of ON bipolar cell (Aim 1). Next, I will examine the possible molecular mechanisms of temporal encoding: intracellular Ca++ increase evoked by mGluR6 signaling (Aim 2), and voltage-gated channels (Aim 3). It has become increasingly difficult to ignore the need for a functional retinal prosthesis and molecular genetics approaches to restore vision for diseased eyes. The proposed study will improve our understanding of parallel processing in the retinal network, which will contribute to the future design of a functional retinal prosthesis and sight restoring gene therapies.

Public Health Relevance

Understanding retinal signal processing will contribute to the development of therapies for restoring vision in many ways. However, the visual system comprises an extremely complex neural network, and visual system function has still been poorly elucidated. The current proposal will advance the understanding of visual signal processing, and thus contribute to restoring vision for patients.

National Institute of Health (NIH)
National Eye Institute (NEI)
Research Project (R01)
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Biology and Diseases of the Posterior Eye Study Section (BDPE)
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Greenwell, Thomas
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Wayne State University
Anatomy/Cell Biology
Schools of Medicine
United States
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Hellmer, Chase B; Clemons, Melissa Rampino; Nawy, Scott et al. (2018) A group I metabotropic glutamate receptor controls synaptic gain between rods and rod bipolar cells in the mouse retina. Physiol Rep 6:e13885
Hellmer, Chase B; Ichinose, Tomomi (2018) Functional and Morphological Analysis of OFF Bipolar Cells. Methods Mol Biol 1753:217-233
Farshi, Pershang; Fyk-Kolodziej, Bozena; Krolewski, David M et al. (2016) Dopamine D1 receptor expression is bipolar cell type-specific in the mouse retina. J Comp Neurol 524:2059-79
Hellmer, C B; Zhou, Y; Fyk-Kolodziej, B et al. (2016) Morphological and physiological analysis of type-5 and other bipolar cells in the Mouse Retina. Neuroscience 315:246-58
Ichinose, Tomomi; Hellmer, Chase B (2016) Differential signalling and glutamate receptor compositions in the OFF bipolar cell types in the mouse retina. J Physiol 594:883-94
Hellmer, Chase B; Ichinose, Tomomi (2015) Recording light-evoked postsynaptic responses in neurons in dark-adapted, mouse retinal slice preparations using patch clamp techniques. J Vis Exp :
Ichinose, Tomomi; Fyk-Kolodziej, Bozena; Cohn, Jesse (2014) Roles of ON cone bipolar cell subtypes in temporal coding in the mouse retina. J Neurosci 34:8761-71
Fyk-Kolodziej, Bozena; Hellmer, Chase B; Ichinose, Tomomi (2014) Marking cells with infrared fluorescent proteins to preserve photoresponsiveness in the retina. Biotechniques 57:245-53
Ichinose, Tomomi; Lukasiewicz, Peter D (2012) The mode of retinal presynaptic inhibition switches with light intensity. J Neurosci 32:4360-71