Our team investigates glutamatergic systems in normal and pathological brains of rodent and humans.

• Glutamate is the major excitatory transmitter in the brain. Before its exocytotic release glutamate is uploaded inside synaptic vesicles by carriers named VGLUT1-3. These transporters are key anatomical and functional markers of glutamatergic transmission 1.
• VGLUTs are distributed in distinct neuronal populations. VGLUT1 and VGLUT2 are synthesized by glutamatergic neurons from cortical and subcortical areas 2. Surprisingly, VGLUT3 is expressed by cholinergic interneurons from the striatum, subpopulation of GABAergic interneurons from the cortex and the hippocampus and in serotoninergic neurons 3. This distribution suggested the existence of glutamate cotransmission with acetylcholine (Ach) or 5-HT or even GABA and brought up numerous questions on the physiological and pathophysiological implication of VGLUT3 1.
• Our major objective is to understand the functional implication of glutamatergic systems in the normal and pathological brain.
• Our research is focused on:
1-    Normal and pathological aging
2-    Reward system and addiction
3-    Mood disorders (anxiety, trama)
• We work on rodent (biochemistry, molecular biology, anatomy, electrophysiology, opto and pharmacogenetic, behavior) as well on human (postmortem anatomy, genetic).
• We hope that this program will help to increase our understanding of the mammalian brain and also open new avenue for the treatment of brain disorders.

Videos

We recently published article entitled, “Cholinergic dysfunction in the dorsal striatum promotes habit formation and maladaptive eating,” which has also been adapted as a graphical abstract and a video abstract that you can check out below.

References

1.    El Mestikawy, S., Wallen-Mackenzie, A., Fortin, G.M., Descarries, L. & Trudeau, L.E. From glutamate co-release to vesicular synergy: vesicular glutamate transporters. Nat Rev Neurosci 12, 204-216 (2011).
2.    Herzog, E., et al. The existence of a second vesicular glutamate transporter specifies subpopulations of glutamatergic neurons. The Journal of neuroscience : the official journal of the Society for Neuroscience 21, RC181 (2001).
3.    Gras, C., et al. A third vesicular glutamate transporter expressed by cholinergic and serotoninergic neurons. The Journal of neuroscience : the official journal of the Society for Neuroscience 22, 5442-5451 (2002).
4.    Gras, C., et al. The vesicular glutamate transporter VGLUT3 synergizes striatal acetylcholine tone. Nat Neurosci 11, 292-300 (2008).

•    Ph. D. in Neurosciences, Université P&M Curie, Paris, France, 1982
•    Habilitation à diriger des recherches, Université P&M Curie, Paris, France, 1991
•    Permanent position at the Centre National de la Recherche Scientifique (CNRS), France, 1983
•    Promoted Chargé de recherche 1ère classe, 1987
•    Promoted Directeur de recherche 2ième classe, 1995
•    Professor, McGill University (Canada Research Chair), 2008
•    Promoted Directeur de recherche 1ère classe, 2012
•    1978-1979, Laboratoire de Biochimie Cellulaire, Collège de France, Paris, Master of Science
•    1979-1985 INSERM U114, Collège de France, Paris, PhD
•    1985-1990 INSERM U288, Faculté de Médecine Pitié-Salpêtrière, Paris,
•    1990-1992 Dept of Cell Biology, Duke University, Durham, NC, USA, Postdoctoral training
•    1992-1998 INSERM U288, Faculté de Médecine Pitié-Salpêtrière, Paris,
•    1998- 2007 INSERM U513, Faculté de Médecine de Créteil, France
•    2007- Currently INSERM U952, CNRS UMR 7224, UPMC, Paris
•    2008- Currently, Douglas Research Center, Dept of Psychiatry, McGill University, Montreal, Canada

Caroline Fasano (research assistant)
Mathieu Favier (Postdoc)
Diana Sakae (Postdoc)
Maya Marcus-Sells (PhD)
Julia Pedersen (PhD, cosupervision Asa Mackenzie Upsala Sweden)
Érika Vigneault (Technician/lab manager)
Eve-Marie Charbonneau (Technician)

• Favier M, Janickova H, Justo D, Kljakic O, Runtz L, Natsheh JY, Pascoal TA, Germann J, Gallino D, Kang JI, Meng XQ, Antinora C, Raulic S, Jacobsen JP, Moquin L, Vigneault E, Gratton A, Caron MG, Duriez P, Brandon MP, Neto PR, Chakravarty MM, Herzallah MM, Gorwood P, Prado MA, Prado VF, El Mestikawy S. Cholinergic dysfunction in the dorsal striatum promotes habit formation and maladaptive eating. The Journal of clinical investigation 2020; PMID:33164988.
• Sakae DY, Ramet L, Henrion A, Poirel O, Jamain S, El Mestikawy S, Daumas S. Differential expression of VGLUT3 in laboratory mouse strains: Impact on drug-induced hyperlocomotion and anxiety-related behaviors. Genes, brain, and behavior 2019;18(3):e12528. PMID:30324647.
• Vigneault É, Poirel O, Riad M, Prud’homme J, Dumas S, Turecki G, Fasano C, Mechawar N, El Mestikawy S. Distribution of vesicular glutamate transporters in the human brain. Frontiers in neuroanatomy 2015;9:23. PMID:25798091.
• El Mestikawy S, Wallén-Mackenzie A, Fortin GM, Descarries L, Trudeau LE. From glutamate co-release to vesicular synergy: vesicular glutamate transporters. Nature reviews. Neuroscience 2011;12(4):204-216. PMID:21415847.
• Herzog E, Nadrigny F, Silm K, Biesemann C, Helling I, Bersot T, Steffens H, Schwartzmann R, Nägerl UV, El Mestikawy S, Rhee J, Kirchhoff F, Brose N. In vivo imaging of intersynaptic vesicle exchange using VGLUT1 Venus knock-in mice. The Journal of neuroscience : the official journal of the Society for Neuroscience 2011;31(43):15544-15559. PMID:22031900.
• Amilhon B, Lepicard E, Renoir T, Mongeau R, Popa D, Poirel O, Miot S, Gras C, Gardier AM, Gallego J, Hamon M, Lanfumey L, Gasnier B, Giros B, El Mestikawy S. VGLUT3 (vesicular glutamate transporter type 3) contribution to the regulation of serotonergic transmission and anxiety. The Journal of neuroscience : the official journal of the Society for Neuroscience 2010;30(6):2198-2210. PMID:20147547.
• Kashani A, Lepicard E, Poirel O, Videau C, David JP, Fallet-Bianco C, Simon A, Delacourte A, Giros B, Epelbaum J, Betancur C, El Mestikawy S. Loss of VGLUT1 and VGLUT2 in the prefrontal cortex is correlated with cognitive decline in Alzheimer disease. Neurobiology of aging 2008;29(11):1619-1630. PMID:17531353.
• Gras C, Amilhon B, Lepicard EM, Poirel O, Vinatier J, Herbin M, Dumas S, Tzavara ET, Wade MR, Nomikos GG, Hanoun N, Saurini F, Kemel ML, Gasnier B, Giros B, El Mestikawy S. The vesicular glutamate transporter VGLUT3 synergizes striatal acetylcholine tone. Nature neuroscience 2008;11(3):292-300. PMID:18278042.
• Kashani A, Betancur C, Giros B, Hirsch E, El Mestikawy S. Altered expression of vesicular glutamate transporters VGLUT1 and VGLUT2 in Parkinson disease. Neurobiology of aging 2007;28(4):568-578. PMID:16563567.
• Gras C, Herzog E, Bellenchi GC, Bernard V, Ravassard P, Pohl M, Gasnier B, Giros B, El Mestikawy S. A third vesicular glutamate transporter expressed by cholinergic and serotoninergic neurons. The Journal of neuroscience : the official journal of the Society for Neuroscience 2002;22(13):5442-5451. PMID:12097496.