About 15 types of retinal ganglion cell, each type tuned to different aspects of the visual scene, independently sample the visual space. About half are coupled via gap junctions to amacrine cells and/or their neighboring ganglion cells of the same type. Very few of these ganglion cell types are well characterized with regard to either their function or what other cells they contact to form their individual circuit. The PI has developed usage of a gap junctional-permeant fluorescent tracer (Hoshi and Mills, 2006) that allows in vivo identification of cells electrically coupled to the injected cell. This tracer, PoPro1, provides the PI with a unique opportunity to examine the properties of coupled ganglion and amacrine cells. This proposal uses this novel technique to investigate this important, but almost completely-unexplored feature of network coupling, namely, the functional consequences of heterologous coupling between amacrine and ganglion cells. The proposal involves (1) recording from a ganglion cell type called the G3 ganglion cell, which preliminary data shows has an orientation bias and determining how this function arises, and (2) discovering the manner in which amacrine cells coupled to ganglion cells participate in synchronized firing of ganglion cells. Synchrony is emerging as an important process in coding and possibly decoding of visual signals. The processes that lead to synchrony are also important in pathologies such as seizures.

Public Health Relevance

The studies in this grant are directed toward two elements pertinent to public health: ganglion cell circuits and gap junctions. The importance of gap junctions has been established in photoreceptor death (the "bystander" effect), but as the extent and function of gap junctions in ganglion cell circuitry is not well known, the involvement of gap junctions in ganglion cell death in diseases such as glaucoma is a topic worthy of investigation.

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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University of Texas Health Science Center Houston
Schools of Medicine
United States
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Marshak, David W; Mills, Stephen L (2014) Short-wavelength cone-opponent retinal ganglion cells in mammals. Vis Neurosci 31:165-75
Hoshi, Hideo; Tian, Lian-Ming; Massey, Stephen C et al. (2013) Properties of the ON bistratified ganglion cell in the rabbit retina. J Comp Neurol 521:1497-509
Hoshi, Hideo; Tian, Lian-Ming; Massey, Stephen C et al. (2011) Two distinct types of ON directionally selective ganglion cells in the rabbit retina. J Comp Neurol 519:2509-21
Hoshi, Hideo; Mills, Stephen L (2009) Components and properties of the G3 ganglion cell circuit in the rabbit retina. J Comp Neurol 513:69-82
Pan, Feng; Mills, Stephen L; Massey, Stephen C (2007) Screening of gap junction antagonists on dye coupling in the rabbit retina. Vis Neurosci 24:609-18
Sarthy, V; Hoshi, H; Mills, S et al. (2007) Characterization of green fluorescent protein-expressing retinal cells in CD 44-transgenic mice. Neuroscience 144:1087-93
Mills, Stephen L; Xia, Xiao-Bo; Hoshi, Hideo et al. (2007) Dopaminergic modulation of tracer coupling in a ganglion-amacrine cell network. Vis Neurosci 24:593-608
Hoshi, Hideo; O'Brien, John; Mills, Stephen L (2006) A novel fluorescent tracer for visualizing coupled cells in neural circuits of living tissue. J Histochem Cytochem 54:1169-76
Zhang, Jian; Li, Wei; Hoshi, Hideo et al. (2005) Stratification of alpha ganglion cells and ON/OFF directionally selective ganglion cells in the rabbit retina. Vis Neurosci 22:535-49
O'Brien, John; Nguyen, H Bao; Mills, Stephen L (2004) Cone photoreceptors in bass retina use two connexins to mediate electrical coupling. J Neurosci 24:5632-42

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