• E-mail :[email]
  • Phone : +33 4 91 82 81 37
  • Location : Marseille, France
Last update 2011-03-31 14:39:30.807

Olivier Manzoni Physiopathogy of Synaptic Transmission & Plasticity

Course and current status

Degrees

  • 1992: Ph.D. Biochemistry, Molecular and Cellular Biology, Université de Montpellier 2.

 

 Career

  • Tenure Position « Chargé de Recherches CR2 » INSERM 1993
  • 1993-1995: Post-Doctoral Fellow, University of California San Francisco (USA). Department of Pharmacology and Physiology in Dr. R.A Nicoll laboratory. Synaptic plasticity in the hippocampus. INSERM post-doctoral fellow 1993-1994.
  • 1997-1999: Visiting Scientist, Vollum Institute (Portland, OR, USA) in Dr. J. Williams’ laboratory. Synaptic plasticity induced by chronic morphine treatment in the Ventral tegmental area and the hippocampus. NIDA/INVEST fellow.
  • Promoted Chargé de Recherches CR1 INSERM 1998
  • Promoted Directeur de Recherches DR2 INSERM 2002.
  • Promoted Directeur de Recherches DR1 INSERM 2010.

 

 Direction appointments

  • 2002: Group Leader Equipe AVENIR INSERM Bordeaux.
  • 2005: Funding Group Leader INSERM U862 Bordeaux.
  • 2010: Team Physiopathology of Synaptic Plasticity (Co-direction: O. Manzoni & P. Chavis) Institut de Neurobiologie de la Mediterranée INMED INSERM U901 Marseille.

 

 Technical expertise

  • Electrophysiology
  • Imaging
  • Synaptopathology.

 

 Relationships with Pharmaceutical companies

  • SANOFI-AVENTIS: Consultant 2007-2008-2009.
  • Scientiae: Consultant 2007-2008.

 

 Member of Editorial board

  • The Journal of Neuroscience: Associate Editor.
  • Neuropharmacology: Editor.
  • PLoS ONE: Academic Editor.

 

 Referee

  • Neuron
  • Nature Neuroscience
  • Proceedings of the National Academy of Sciences (U.S.A.)
  • Journal of Neuroscience (listed “Frequent reviewer”)
  • Biological Psychiatry
  • Journal of Neurophysiology
  • Trends in Neurosciences
  • Learning and Memory
  • Journal of Physiology
  • Neuropharmacology
  • Neuropsychopharmacology
  • European Journal of Neuroscience
  • Molecular Pharmacology
  • Brain Research
  • Journal of Neurochemistry
  • Journal of Pharmacology and Experimental Therapeutics
  • Molecular Pharmacology 
  • PLoS ONE 

 

 Grant Committees and research orientation

  • Comité Evaluation ANR Blanc 2011.
  • Commission de Spécialistes n° 69 Neuroscience Université de Bordeaux II, 2007 & 2009.
  • Comité AERES/INSERM 2008.
  • Welcome Trust.
  • Medical Research Council.
  • Agence Nationale de la Recherche, ANR Blanc 2011.
  • Ville de Paris.
  • Région PACA.
  • Fondation pour la Recherche sur le Cerveau. 

 

 Scientific Societies

  • Société Française des Neurosciences
  • Society For Neurosciences USA

 

 Teaching Activities at the University of Bordeaux 2

  • Master 2: 2007 & 2008
  • PENS School: Synapse Summer School Bordeaux 2008-2009.

 

 Award

  • 1997 :  NIDA/INVEST Fellowship.
  • 2010:   NARSAD Independent Investigator.

 

 Best publications since the beginning of the career

1. Lafourcade M, Larrieu L, Susana Mato4#, Anais Duffaud2,3, Marja Sepers1,3, Matias I, De Smedt V, Labrousse V, Bretillon L, Matute C,Rodríguez-Puertas R, Layé S, Manzoni O.J. (2011) Nature Neuroscience., Published online 30-01-2011.

Nutritional Omega-3 deficiency abolishes endocannabinoid mediated neuronal functions.

2. Kasanetz F., Deroche-Gamonet V, Berson N, Balado E, Lafourcade M, Manzoni* O.J., & Piazza* PV (2010) * Shared seniority. Transition to addiction is associated with a persistent impairment in synaptic plasticity Science Jun 25;328(5986):1709-12.

3. Mikasova L, Groc L, Choquet D, Manzoni OJ, (2008) Altered surface trafficking of presynaptic cannabinoid type 1 receptor in and out synaptic terminals parallels receptor desensitization. Proc Natl Acad Sci U S A. track II 25;105(47):18596-601.

4. Mato S, Chevaleyre V, Robbe D, Pazos A, Castillo PE, & Manzoni OJ (2004) A single in-vivo exposure to delta 9THC blocks endocannabinoid-mediated synaptic plasticity Nature Neuroscience 7, 585-586.

5. Robbe D, Kopf M, Remaury A, Bockaert J, & Manzoni OJ (2002) Endogenous cannabinoids mediate long-term synaptic depression in the nucleus accumbens Proc Natl Acad Sci U S A track II 99, 8384-8388 

6. Manzoni OJ, Manabe T, & Nicoll RA (1994) Release of adenosine by activation of NMDA receptors in the hippocampus Science 265, 2098-2101.

7. Williams JT, Christie MJ, & Manzoni O (2001) Cellular and synaptic adaptations mediating opioid dependence Physiological Review 81, 299-343.

8. Chavis P, Mollard P, Bockaert J, & Manzoni O (1998) Visualization of cyclic AMP-regulated presynaptic activity at cerebellar granule cells Neuron 20, 773-781.

9. Manzoni O, Prezeau L, Marin P, Deshager S, Bockaert J, & Fagni L (1992) Nitric oxide-induced blockade of NMDA receptors Neuron 8, 653-662.



Scientific summary

Past activity:

Our team has been focusing on the understanding of the molecular basis of synaptic plasticity of glutamatergic synapses in normal and pathological conditions. Glutamatergic synapses participate to crucial brain functions (e.g. memory, cognition, reward) and their plasticity mediates structural and functional rearrangements involving multiple pre and post-synaptic integration systems among which we have chosen two trans-synaptic systems: the endocannabinoid (group leader: O.Manzoni, Ph.D.) and the Cell Adhesion Molecules/Extracellular Matrix (ECM) system (group leader: P. Chavis, Ph.D.). Using a combination of cellular biology, biochemistry, electrophysiology and optical techniques, our goals were to identify metaplastic adaptations in synaptic plasticity and to elucidate the roles of Reelin in post-natal neuronal network maturation. We have made three main discoveries. 1/ We have made a major conceptual advance in the field of addiction by presenting the first evidence that in cocaine addicted rats allostatic adaptations keep synapses in a state of non-plasticity while on the contrary, homeostatic adaptations allow the recovery of plasticity in non-addicted rats. 2/ We also discovered that the surface dynamics of the most abundant G-protein coupled receptor (GPCR) of the CNS, the CB1R are altered following exposure to psychoactive cannabinoid and based on our work proposed a general desensitization mechanism for GPCRs. 3/ We have elucidated a molecular mechanism leading to the postnatal maturation of synapses in the hippocampus. Thus, we found that reelin, an ECM protein involved in the etiology of schizophrenia, governs the surface trafficking  and subunit composition of glutamate receptors of NMDA. 

Current research project:

Regulation of mood and emotion is critical for mental health. Major neuropsychiatric disorders including mental retardation (MR), autism, schizophrenia, depression and addiction are accompanied by significant social, emotional and cognitive problems. The neuronal substrates of emotional perturbation are seldom studied in the context of these pathologies. In neuropsychiatric diseases, disruption of a molecular cog of the synaptic machine causes or result in deficits in synaptic plasticity and leads to abnormal information processing. The goal of our project is to unravel synaptic dysfunctions and propose new therapeutic venues for synaptopathies. 
We postulate that in neuropsychiatric diseases the reduction of the range of synaptic plasticity participates to the reduction of cognitive and behavioral flexibility. Pathologies resulting from the dysregulation of synaptic plasticity can be linked to a disruption or insufficiency in the expression of specific gene products and/or to environmental insults. To address these two dimensions of pathological synaptic plasticity and based on our preliminary results we search for alterations of synaptic plasticity in mouse models of schizophrenia, autism, mental retardation, addictive drugs and dietary deficiency. Based on the knowledge gained in the previous aims, we will use already available and newly developed pharmacological agents and nutritional strategies acting on neurotransmitter systems and/or transduction pathways to restore normal synaptic plasticity and behaviors in diseased mice.  
Image d’exemple