Associate Professor Ophthalmology & Visual Science, Medical School
Areas of Interests
- Research Interest
- Molecular mechanisms of electrical synapse regulation in the vertebrate CNS
Molecular mechanisms of electrical synapse regulation in the vertebrate CNS
Synaptic plasticity in the central nervous system entails a wide variety of mechanisms, encompassing both chemical and electrical synapses. Electrical synapses, composed of gap junctions, are a key component of neural circuitry throughout the CNS. Nowhere is this more apparent than in the vertebrate retina, where gap junctions play critical roles in neural processing. These include reducing noise at photoreceptor synapses, establishing receptive field sizes of many neurons, coordinating firing of spiking neurons, and establishing oscillations in neural networks. These functions are closely controlled during light adaptation, influencing the sensitivity and resolution of the retina, and accounting for a large part of the network plasticity.
A major focus of work in my lab is on revealing the molecular mechanisms that control network adaptation in the retina. Our previous work in this area included the discovery of the first predominantly neuron-specific gap junction protein (connexin 35), which is widely expressed throughout the retina and brain. We are examining how protein kinases and other cellular pathways modulate the opening and permeability of these gap junction channels, and how light adaptation drives these pathways.
A tutorial in my lab would provide a broad-based experience in cellular and molecular neuroscience. Research projects may include in vitro molecular and biochemical studies, confocal immunofluorescence microscopy, and transgenic zebrafish studies.
- Shiller SM, Konduri K, Harshman LK, Welch BJ, O’Brien JC. Recurrent thyroid cancer with changing histologic features. Proc (Bayl Univ Med Cent). 2010 Jul;23(3):304-10.
- Maddox WT, Glass BD, O’Brien JB, Filoteo JV, Ashby FG. Category label and response location shifts in category learning. Psychol Res. 2010 Mar;74(2):219-36.
- Li H, Chuang AZ, O’Brien J. Photoreceptor coupling is controlled by connexin 35 phosphorylation in zebrafish retina. J Neurosci. 2009 Dec 2;29(48):15178-86.
- Kothmann WW, Massey SC, O’Brien J. Dopamine-stimulated dephosphorylation of connexin 36 mediates AII amacrine cell uncoupling. J Neurosci. 2009 Nov 25;29(47):14903-11.
- O’Brien JC, Shiller SM, Cusick MG, Hamman BL. Mass in the neck after radiation exposure from Chernobyl disaster. Proc (Bayl Univ Med Cent). 2009 Apr;22(2):156-61. No abstract available.
- Patel, L.S., Mitchell, C.K., Dubinsky, W.P., and O’Brien, J. (2006) Regulation of gap junction coupling through the neuronal connexin Cx35 by nitric oxide and cGMP. Cell Commun. Adhes. 13(1-2): 41-54.
- Ouyang, X., Winbow, V.W., Patel, L.S., Burr, G.S., Mitchell, C.K., and O’Brien, J. (2005) Protein kinase A mediates reversible regulation of electrical synapses containing connexin35 through a complex pathway. Mol. Brain Res. 135(1-2): 1-11.
- Burr, G.S., Mitchell, C.K., Keflemariam, Y.J., Heidelberger, R., and O’Brien, J. (2005) Calcium-dependent binding of calmodulin to retinal gap junction proteins. Biochem. Biophys. Res. Comm. 335: 1191-1198.
- O’Brien, J., Nguyen, H.B., and Mills, S.L. (2004) Cone photoreceptors in bass retina use two connexins to mediate electrical coupling. J. Neurosci. 24(24): 5632-5642.
- Pereda, A., O’Brien, J., Nagy, J.I., Smith, F., Bukauskas, F., Davidson, K.G.V., Kamasawa, N., Yasumura, T., and Rash, J.E. (2003) Short-range functional interaction between connexin35 and neighboring chemical synapses. Cell Comm. Adhes. 10: 419-423.
- Pereda, A., O’Brien, J., Nagy, J.I., Bukauskas, F., Davidson, K.G.V., Yasumura, T., and Rash, J.E. (2003) Connexin35 mediates electrical transmission at mixed synapses on Mauthner cells. J. Neurosci. 23(20): 7489-7503.
- Mills, S.L., O’Brien, J.J., Li, W., O’Brien, J., and Massey, S.C. (2001) Rod pathways in the mammalian retina utilize connexin 36. J. Comp. Neurol. 436: 336-350.