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.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY012857-11
Application #
8244508
Study Section
Biology and Diseases of the Posterior Eye Study Section (BDPE)
Program Officer
Greenwell, Thomas
Project Start
2000-02-01
Project End
2014-03-31
Budget Start
2012-04-01
Budget End
2013-03-31
Support Year
11
Fiscal Year
2012
Total Cost
$360,000
Indirect Cost
$120,000
Name
University of Texas Health Science Center Houston
Department
None
Type
Schools of Medicine
DUNS #
800771594
City
Houston
State
TX
Country
United States
Zip Code
77225
O'Brien, John (2014) The ever-changing electrical synapse. Curr Opin Neurobiol 29:64-72
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
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
Rash, John E; Curti, Sebastian; Vanderpool, Kimberly G et al. (2013) Molecular and functional asymmetry at a vertebrate electrical synapse. Neuron 79:957-69
Palacios-Prado, Nicolas; Hoge, Gregory; Marandykina, Alina et al. (2013) Intracellular magnesium-dependent modulation of gap junction channels formed by neuronal connexin36. J Neurosci 33:4741-53
O'Brien, Jennifer J; Chen, Xiaoming; Macleish, Peter R et al. (2012) Photoreceptor coupling mediated by connexin36 in the primate retina. J Neurosci 32:4675-87
Vila, Alejandro; Satoh, Hiromasa; Rangel, Carolina et al. (2012) Histamine receptors of cones and horizontal cells in Old World monkey retinas. J Comp Neurol 520:528-43
Pan, Feng; Keung, Joyce; Kim, In-Beom et al. (2012) Connexin 57 is expressed by the axon terminal network of B-type horizontal cells in the rabbit retina. J Comp Neurol 520:2256-74
Kothmann, W Wade; Massey, Stephen C; O'Brien, John (2009) Dopamine-stimulated dephosphorylation of connexin 36 mediates AII amacrine cell uncoupling. J Neurosci 29:14903-11
Li, Hongyan; Chuang, Alice Z; O'Brien, John (2009) Photoreceptor coupling is controlled by connexin 35 phosphorylation in zebrafish retina. J Neurosci 29:15178-86

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