BSc Honours (U. Ottawa, 1994),
PhD (McGill, 2001)
PostDoc (Ottawa Health Research Institute, 2004)
|Teaching & Research
developmental neurobiology, retina, sodium channel, Na(v)1.6, optic nerve, multiple sclerosis.
am interested in several aspects of the development and function of the nervous system in both health and disease. My group uses the mammalian retina to study neuronal biology because of its extensive postnatal development, layered cellular architecture, relatively simple circuitry, and accessibility. Indeed, because of these features, the retina is probably the best characterized part of the central nervous system. Here are two projects that are ongoing in my laboratory.
Role of a voltage gated sodium channel in retina development
Mice that have a mutation in Scn8a, the gene that encodes the voltage-gated sodium channel Na(v)1.6, have dramatically reduced retinal function according to electroretinogram (ERG) recordings (Côté et al, 2005; Smith and Côté, 2012). Interestingly, the visual defect originates at the level of the photoreceptors, the cells of the retina that initially capture light.
Role of the voltage-gated sodium channel Nav1.6 in neuronal death following
Voltage gated sodium channels (VGSCs) allow sodium to enter a cell in response to a reduction of the voltage across the cell membrane and are essential for the generation of the nerve impulse. In multiple sclerosis the usually tightly regulated placement and concentration of VGSCs along the axon is profoundly altered following demyelination. It is believed that an increase in Na(v)1.6, a type of VGSC that has a strong ability to allow persistent sodium entry, is an important factor in eventual neuron death.
Smith BJ, Côté PD, Tremblay F. D1 Dopamine receptors modulate cone ON bipolar cell Nav channels to control daily rhythms in photopic vision, Chronobiol Int. IN PRESS
Smith BJ, Wang X, Chauhan BC, Côté PD, Tremblay F. (2014) Contribution of retinal ganglion cells to the mouse electroretinogram. Doc Ophthalmol. 128: 155-168.
Smith BJ, Tremblay F, Côté PD. (2013) Voltage-gated sodium channels contribute to the b-wave of the rodent electroretinogram by mediating input to rod bipolar cell
Murphy JP, Côté PD, Pinto D. (2012) Monitoring the Switch: The Warburg Effect and Targeted Proteomic Analysis of Cancer Metabolism. Curr Proteomics. 9 (1): 26-39.
Smith BJ , Côté PD (2012) Reduced Retinal Function in the Absence of Nav1.6. PLoS ONE 7(2): e31476. doi:10.1371/journal.pone.0031476
Ichikawa H, Kano M, Shimizu Y, Suzuki T, Sawada E, Ono W, Chu LW, Côté PD. (2010) Increase of c-Fos and c-Jun expression in spinal and cranial motoneurons of the degenerating muscle mouse (Scn8a(dmu)). Cell Mol Neurobiol. 30(5): 737-42.
Shafey D, Côté PD, De Repentigny Y, Kothary R. (2005) siRNA mediated knockdown of the Survival of Motor Neuron (Smn) protein in cell culture and in transgenic mice. Exp Cell Res 311(1): 49-61.
Côté PD, De Repentigny Y, Coupland SG, Schwab Y, Roux M, Levinson SR, Kothary R. (2005) Physiological maturation of photoreceptors depends on the voltage-gated sodium channel NaV1.6 (Scn8a). J Neurosci. 25 (20): 5046-50.
Côté PD, Moukhles H, Carbonetto S. (2002) Dystroglycan is not required for localization of dystrophin, syntrophin, and neuronal nitric-oxide synthase at the sarcolemma but regulates integrin alpha 7B expression and caveolin-3 distribution. J Biol Chem. 277 (7): 4672-9.
De Repentigny Y, Côté PD, Pool M, Bernier G, Girard S, Vidal
SM, Kothary R.
Jacobson C, Côté PD, Rossi SG, Rotundo RL, Carbonetto S. (2001) The dystroglycan complex is necessary for stabilization of acetylcholine receptor clusters at neuromuscular junctions and formation of the synaptic basement membrane. J Cell Biol. 152 (3): 435-50.
Côté PD, Moukhles H, Lindenbaum M, Carbonetto S. (1999) Chimaeric mice deficient in dystroglycans develop muscular dystrophy and have disrupted myoneural synapses. Nat Genet. 23 (3): 338-42. SEE ALSO NEWS AND VIEWS ARTICLE: Chamberlain J (1999) The dynamics of dystroglycan Nat Genet. 23 (3): 256-8.