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.
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.
|Vila, Alejandro; Whitaker, Christopher M; O'Brien, John (2016) Membrane-associated guanylate kinase scaffolds organize a horizontal cell synaptic complex restricted to invaginating contacts with photoreceptors. J Comp Neurol :|
|Yoshikawa, Shunichi; Vila, Alejandro; Segelken, Jasmin et al. (2016) Zebrafish connexin 79.8 (Gja8a): A lens connexin used as an electrical synapse in some neurons. Dev Neurobiol :|
|Curti, Sebastian; O'Brien, John (2016) Characteristics and plasticity of electrical synaptic transmission. BMC Cell Biol 17 Suppl 1:13|
|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|
|Moore, Keith B; O'Brien, John (2015) Connexins in neurons and glia: targets for intervention in disease and injury. Neural Regen Res 10:1013-7|
|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|
|Li, Hongyan; Chuang, Alice Z; O'Brien, John (2014) Regulation of photoreceptor gap junction phosphorylation by adenosine in zebrafish retina. Vis Neurosci 31:237-43|
|O'Brien, John (2014) The ever-changing electrical synapse. Curr Opin Neurobiol 29:64-72|
|Li, Hongyan; Zhang, Zhijing; Blackburn, Michael R et al. (2013) Adenosine and dopamine receptors coregulate photoreceptor coupling via gap junction phosphorylation in mouse retina. J Neurosci 33:3135-50|
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