Research interest

Our lab investigates the cellular and molecular mechanisms used by neurons to decode synaptic and electrical
GFP-tagged protein in a hippocampal neuron. © Copyright 2004, Paul De Koninck. All rights reserved.
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.

Technical approaches

We combine several techniques to study these questions:
  • Neuronal tissue culture (dissociated cultures or brain slices).
    Dissociated culture of hippocampal neurons. © Copyright 2004, Paul De Koninck. All rights reserved. This image used to be called neuron_culture_800px.jpg
  • Advanced imaging techniques of high spatial and temporal resolution: Confocal microscopy,  wide field video-microscopy, single molecule imaging, Fluorescence Recovery After Photobleaching (FRAP), Fluorescence Lifetime Imaging (FLIM) and Forster Resonance Energy Transfer (FRET) to monitor dynamic changes in second messenger signals (e.g. calcium), protein translocation and diffusion and protein-protein interactions in neurons and their synapses.
  • Electrophysiological recordings (patch-clamping) to study the functional impact of the molecular reorganization at synapses.
  • Molecular Biology to develop imaging tools, such as genetically engineered biosensors and FP-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.

Environment

Our lab is in the division of Cellular Neurobiology at the Centre de recherche de l'Institut universitaire en santé mentale de Québec (CRIUSMQ). We collaborate and share equipment and facilities with several members of this division, as well as with the division of Systems Neurobiology. The CRIUSMQ is part of several Research Centers in the Laval University community in Quebec City.

Neurophotonic Center

Within the CRIUSMQ is located the Neurophotonic Center, a unique transdisciplinary facility equipped with advanced and custom-designed optical systems for cellular and in vivo imaging of neuronal signaling and communication. Several labs and   laser, photodetection, nanopositioning and microscopy technology to improve existing approaches, and develop new ones for cellular imaging and microintervention in live brain tissue.

Biophotonics Graduate Program

Laval University offers the first and only graduate Programs (MSc and PhD) in Biophotonics in Canada (www.biophotonics.ulaval.ca). The programs, supported by a CREATE training grant from NSERC (Training Program in Biophotonics), train students with undergraduate backgrounds in either Life sciences, physics, chemistry, or engineering. All trainees in the Program are co-supervised by mentors from both the Life Sciences and the Physical Sciences/Engineering. Several trainees in the lab are enrolled in the Biophotonics Training Program.

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.

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