Electrical coupling mediated by gap junctions contributes to the signal processing functions of most types of retinal neurons. Modulation of gap junctions during visual adaptation has profound effects on sensitivity and receptive field properties of many neurons and influences the path of signal flow in the mammalian rod circuit. The long-term objectives of this study are to identify the mechanisms that regulate electrical coupling in the retina, and to determine which modes of regulation are most important for the adaptive processes observed in different electrically coupled neural circuits. Previous results have indicated that phosphorylation of gap junction proteins is a critical mechanism to regulate coupling. Phosphorylation of connexin 35/36 (Cx35/36) gap junctions changes dynamically with light adaptation and correlates directly with coupling. In this project, we will examine the profoundly different signaling mechanisms that control coupling through Cx35/36 gap junctions in AII amacrine cells and photoreceptors. We will identify the key molecular components that couple and uncouple the gap junctions in these two systems, and examine the factors that contribute to the assembly of these different signaling modules. This research will shed light on the fundamental mechanisms that control electrical coupling, and reveal signaling pathways that may be defective in visual disorders.

Public Health Relevance

This project examines fundamental mechanisms that control cell-to-cell communication and the establishment of neural networks in the retina and throughout the central nervous system. It will reveal processes that play important roles in neural network functions that affect visual acuity and light adaptation, memory formation, and motor coordination. The study will reveal signaling pathways that may be targets for intervention in disorders linked to these network functions including macular degeneration, epilepsy, and hearing loss.

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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O'Brien, John; Bloomfield, Stewart A (2018) Plasticity of Retinal Gap Junctions: Roles in Synaptic Physiology and Disease. Annu Rev Vis Sci 4:79-100
O'Brien, John (2017) Design principles of electrical synaptic plasticity. Neurosci Lett :
Yoshikawa, Shunichi; Vila, Alejandro; Segelken, Jasmin et al. (2017) Zebrafish connexin 79.8 (Gja8a): A lens connexin used as an electrical synapse in some neurons. Dev Neurobiol 77:548-561
Miller, Adam C; Whitebirch, Alex C; Shah, Arish N et al. (2017) A genetic basis for molecular asymmetry at vertebrate electrical synapses. Elife 6:
Vila, Alejandro; Whitaker, Christopher M; O'Brien, John (2017) Membrane-associated guanylate kinase scaffolds organize a horizontal cell synaptic complex restricted to invaginating contacts with photoreceptors. J Comp Neurol 525:850-867
Curti, Sebastian; O'Brien, John (2016) Characteristics and plasticity of electrical synaptic transmission. BMC Cell Biol 17 Suppl 1:13
Sun, Kaiqi; Zhang, Yujin; D'Alessandro, Angelo et al. (2016) Sphingosine-1-phosphate promotes erythrocyte glycolysis and oxygen release for adaptation to high-altitude hypoxia. Nat Commun 7:12086
Rash, J E; Kamasawa, N; Vanderpool, K G et al. (2015) Heterotypic gap junctions at glutamatergic mixed synapses are abundant in goldfish brain. Neuroscience 285:166-93
Wang, Helen Yanran; Lin, Ya-Ping; Mitchell, Cheryl K et al. (2015) Two-color fluorescent analysis of connexin 36 turnover: relationship to functional plasticity. J Cell Sci 128:3888-97
Zhang, Zhijing; Li, Hongyan; Liu, Xiaoqin et al. (2015) Circadian clock control of connexin36 phosphorylation in retinal photoreceptors of the CBA/CaJ mouse strain. Vis Neurosci 32:E009

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