Affiliated with Université Laval & CERVO Research Centre
CERVO Brain Research Centre - 2601 Chemin de la Canardière F-5573 Québec QUEBEC G1J 2G3 Canada
My research aims for a better understanding of the neuronal synaptic plasticity in various physiological and pathological conditions. We are trying to clarify the changes occurring to neurons regarding their inter-connections, their receptor reconfigurations and their interaction with glial cells in such conditions. The objective of our past, present and future discoveries is to develop new advanced and efficient therapeutics to prevent or fight neurological diseases.
[1] The study of synaptic mechanisms in the sensory spinal cord and their plasticity in pathological conditions in experimental models of chronic pain and autism. We have recently shown that promoting neuronal chloride extrusion can rescue and even amplify benzodiazepine site-ligand mediated analgesia (Lorenzo et al., Nature Commun. 2020). This recent advance in benzodiazepine actions occurs via pharmacological actions on both α2/α3GABAA receptor subtypes and KCC2 (a potassium chloride co-transporter maintaining the neuronal resting potential). This discovery, by combining lower dose of benzodiazepine with a potassium/chloride transport enhancer could change the way of dosing and administering benzodiazepines in the future by lowering their effective doses and enlasting their actions. It can even make high benzodiazepine doses more effective. These results constitute an advance in understanding the actions and limitations of benzodiazepines and represent an important upgrade of their therapeutic action in animals and maybe in humans in the future:
Next generations of benzodiazepines: new openings and opportunities?
Les benzodiazépines de la prochaine génération: de nouvelles possibilités ?
[2] The differences in the regulatory mechanisms of GABAA receptors, KCC2 and Calcitonin Gene-Related Peptide(CGRP) between male and female animals (Mapplebeck et al., Cell reports 2019; Paige et al., J. Neurosci. 2022) and between men and women (Dedek et al., Brain 2022):
[3] Hyper-excitability and KCC2: the neuronal interaction between NMDA receptors and KCC2 (with Pr Michael Hildebrand and his team, Dedek et al., Brain 2019).
[4] The chloride homeostasis across the superficial dorsal horn (with Francesco Ferrini et al., Nature Commun. 2020). A gradient of KCC2 and of its activity can be overserved and measured across the spinal superficial dorsal horn. This inconspicuous intracellular Cl- heterogeneity across the superficial dorsal horn neurons critically shapes plasticity for selective nociceptive modalities.The higher propensity to plasticity in lamina I as compared to lamina II differentially affects sensitization to thermal and mechanical input. Further investigations are in progress…
[5] The involvement of multiple immune inflammatory mediators in the CNS or at the periphery, in various diseases. The consequences at the spinal cord and brain levels.
[6] The role of GPCRs (G-Protein Coupled Receptors) like the Neurokinin-1 receptor in nociception and pain transmission (led by Pr Antoine Godin).
In addition to the classical collaborative work between biologists and geneticists, our current projects require close interactions with biophysicists, expert microscopists and mathematicians. We are trying to develop new mathematical and analytical tools which could be broadly applied to biology and neuroscience.
Cellular neurobiology, GABAA receptors, benzodiazepines, glycine receptors, chloride homeostasis, K+/Cl- Cotransporters (NKCC1/KCC2), KCC2 regulation, KCC2 enhancers, spinal cord, sensory and motor physiology, neuronal excitability, synaptic transmission and plasticity, GPCR, Neurokinin-1 receptor, neuropharmacology and drug development.
Chronic pain, autism, neurodegenration, amyotrophic lateral sclerosis
Functional neuronal imaging, immunohisto- and cytochemistry, confocal and electron microscopy, in vivo virology for neuroscience, fluorescence spectroscopy, non-linear microscopy, signal analysis and image analytic tool development, super-resolution microscopy, in vivo and in vitro optogenetics, nanotechnologies, behavioral measurements, neuropharmacology/drug development, preclinical studies, RT-qPCR (Real Time quantitative Polymerase Chain Reaction), RNAscope.
