Our lab investigates the cellular and molecular mechanisms used by neurons to decode synaptic and electrical activities that propagate through neural circuits. We are particularly interested in learning how these mechanisms contribute to synaptic remodeling and to the maintenance and modifications of brain circuit connectivity. Synaptic remodelling in the brain during development and in adult life is thought to represent fundamental cellular processes of learning and memory. However, upon abnormal levels of neural activities, it can lead to severe cognitive deficits. The fine line between the mechanisms that produce constructive versus destructive changes in brain circuit connectivity is largely unknown.

The synaptic signalling model that we study is the Ca²⁺-calmodulin-dependent pathway at excitatory synapses in the rat hippocampus. We study the biochemical properties, structure/function and specific activation of the enzyme CaM kinase II (for Ca²⁺/calmodulin-dependent protein kinase II), which plays several important roles in neural function, such as brain cell development, synaptic function and remodeling, and learning and memory. Our studies are aimed primarily at learning how CaM kinase II decodes Ca²⁺ signals in neurons and modifies synaptic structures and function. For our experiments, we use living neural circuits (dissociated cultures or brain slices). We also use an in vitro approach aimed at deciphering the structure / function of CaM kinase II as a decoder of Ca²⁺ oscillations.

We combine several techniques to study these questions:

-Neuronal tissue culture (dissociated cultures or brain slices).

-Advanced imaging techniques of high spatial and temporal resolution (confocal and wide field microscopy, single particle tracking, FRAP and FRET) to monitor dynamic changes in second messenger signals (e.g. calcium), protein translocation and diffusion and protein-protein interactions at the synapses.

-Electrophysiological recordings (patch-clamping and multi-electrode arrays ) to study the functional impact of the molecular reorganization at synapses. Molecular Biology to develop imaging tools, such as genetically engineered biosensors and GFP-tagged proteins and to manipulate expression of specific genes in cultured neurons.

-Biochemistry for structure/function studies in vitro and to measure protein expression and modification.

Our lab is in the division of Cellular Neurobiology at the Centre de recherche Université Laval Robert-Giffard (CRULRG). We collaborate and share equipment and facilities with several members of this division, as well as with the division of Systems Neurobiology . The CRULRG is part of several Research Centers in the Laval University community in Quebec City.

Neurophotonic Center

Within the CRULRG is located the Neurophotonic Center, a unique transdisciplinary facility equipped with the latest laser, photodetection, nanopositioning and microscopy technology to improve existing approaches, and develop new ones for cellular imaging and microintervention in live brain tissue.

Setting New Frontiers in Neuroscience with Material Sciences and Photonics

Our lab is part of a transdisciplinary group of Neuroscientists, Physicists and Chemists whose objective is to develop novel approaches in Material Sciences and Photonics to study brain cells. Our CIHR training grant (www.neurophysics.ca) is targeted to support trainees with a background in Physics or Chemistry in performing research in Neurobiology.

Probing synaptic remodeling with Quantum Dots and Image Correlation Spectroscopy

Our lab has teamed up with the laboratories of Biophysicist Paul Wiseman (McGill) and Physical Chemist Benoit Dubertret (ESPCI, France) to push the limits of resolution of molecular interactions at synapses, using quantum dots as fluorescent labels and Image Correlation Spectroscopy. We have formed a Human Frontier Science Program research team.

Nano-Tools for Neuropharmacology

Our lab is part of a CIHR New Emerging Team, whose objective is to exploit advances in the fields of material sciences and nanotechnology to improve existing, and develop novel tools for the study of basic neuropharmacological mechanisms that determine synaptic function and plasticity.

	Paul De Koninck, Ph.D.
	Francine Nault, research assistant
	Hugues Dufour, research assistant
	Jean-François Labbé, research assistant
	Stéphane Pagès Ph.D. in Physical Chemistry postdoctoral fellow
	Kim Doré, Ph.D. in Chemistry, postdoctoral fellow
	Barthélémy Tournier, Ph.D. in Molecular and Cellular Biology, postdoctoral fellow
	Farida El gaamouch, Ph.D. in Neurosciences, postdoctoral fellow
	Simon Labrecque, Ph.D. student in Physics
	Mado Lemieux, Ph.D. student in Biochemistry
	Christian Tardif, Ph.D. student in Biophotonics
	Olivier Dupont-Therrien, Ph.D. student in Biophotonics
	Étienne Labrie-Dion, M.Sc. student in Neurobiology
	Patrice Dionne, M.Sc. student in Biophotonics
	Nikolas Bernier, M.Sc. student in Neurobiology

Former members of the lab

Positions are open for a Post-doc and a graduate student

Centre de recherche Université Laval Robert-Giffard
Unité de neurobiologie cellulaire
2601 Chemin de la Canardière, Suite F-6500
Québec (Québec) G1J 2G3 (click here to see a map: Google Maps (satellite view))
Canada

Phone: +1-418-663-5747 ext. 4721 (Paul's office), ext. 4722 (lab), ext. 4709 (Francine's office), ext. 4712 (students' room)
Fax: +1-418-663-8756

Our research endeavors are made possible by the following agencies:

Bayer K.-U., LeBel E., McDonald G.L., O'Leary H., Schulman H., De Koninck P.(2006). Transition from reversible to persistent binding of CaMKII to postsynaptic sites and NR2B. J. Neurosci. 26(4): 1164-74

Hudmon, A., LeBel, E., Roy, H., Schulman, H., Waxham, N. & De Koninck, P. (2005). A mechanism for CaMKII clustering at synaptic and non-synaptic sites based on self-association. J. Neurosci. 25: 6971-83

Dupont, G., Houart, G. & De Koninck, P. (2003) Sensitivity of CaM kinase II to the frequency of Ca2+ oscillations: A simple model. Cell Calcium 34: 485-497.

Coull, J.A.M., Boudreau, D., Bachand, K., Prescott, S.A., Nault, F., Sík, A., De Koninck, P. & De Koninck, Y. (2003) Transsynaptic shift in anion gradient in spinal lamina I neurons as a novel mechanism of neuropathic pain. Nature 424: 938-942.

Bayer, K.-U., De Koninck, P. & Schulman, H. (2002). Alternative splicing modulates the frequency-dependent response of CaMKII to Ca²⁺ oscillations. EMBO J. 21: 3590-3597.

Collaborative work with the CIHR Neurophysics, NET and HFSP groups:

Smith, B. A., Roy, H., De Koninck, P., Grütter, P. & De Koninck, Y. (2007). Dendritic spine biomechanics probed with atomic force microscopy. Biophysical Journal. 92:1419-1430.

Costantino, S., Heinze, K.G., Martinez, O.E., De Koninck, P. & Wiseman, P.W. (2005). Two-photon fluorescent micro-lithography for live cell imaging. Microscopy Research and Technique. 68: 272-276.

Thibault, C., Koubassov, V., De Koninck, P., Chin, S.L., De Koninck, Y. (2005). Destruction of polymer growth substrates for cell cultures in two photon microscopy. J. Microscopy. 220:120-127.

Postdoc years:

Bayer, K.-U., De Koninck, P., Leonard, A.S., Hell, J.W. and Schulman, H. (2001). Interaction with the NMDA Receptor locks CaMKII in an Active State. Nature 411: 801-805.

De Koninck, P. & Schulman, H. (1998). Sensitivity of Ca2+/calmodulin-dependent protein kinase II to the frequency of Ca²⁺ oscillations. Science 279: 227-230.

Ph.D. years:

De Koninck, P. & Cooper, E. (1995). Differential regulation of neuronal nicotinic ACh receptor subunit genes in cultured neonatal rat sympathetic neurons: Specific induction of alpha 7 by membrane depolarization through a Ca²⁺/calmodulin-dependent kinase pathway. J. Neurosci. 15: 7966-7978.

De Koninck, P., Carbonetto S. & Cooper, E. (1993). NGF induces neonatal rat sensory neurons to extend dendrites in culture after removal of satellite cells. J. Neurosci. 13: 577-585.