Our team has been created by the will of the two group leaders to assemble a cluster of electrophysiologists of sufficient size and recognized expertise to analyze, in depth, the properties of different biomolecules on cellular excitability at the animal, organ, cell and molecule levels.

Created in 2015 by the fusion of two complementary groups, the new team, directed by Michel Vignes (PU-UM) and Pierre Charnet (DR1 CNRS), is now housed at the Pole Balard, Route de Mende, and manages a series of complementary electrophysiological research themes and expertise.  It is composed of six permanent senior scientists: Valérie Rolland(PU-UM), Jean-Baptiste Thibaud (DR2 CNRS), Thierry Cens (CRN INSERM), Matthieu Rousset (CR1 INSERM), Janique Guiramand (CR1 CNRS 25%), three assistant professors; Marie Céleste de Jesus Ferreira (MCU UM); Julien Roussel (MCU UM); Claudine Ménard (MCU UM), one technician: Catherine COHEN SOLAL (ITRF UM).

Our Themes

The decline in pollinators is partly due to chemical inputs in the environment. Analysis of water, crops, beeswax and honey shows the presence of several pesticides: herbicides, fungicides and anti-parasitic insecticides. Their deleterious effects on beneficial insects are assessed by mortality tests (LD50), but little is known about their impact on insect physiology at low doses. Even for the most widely used neurotoxic insecticides, only the effects on their presumed molecular targets (e.g. NaV for pyrethroids) are assessed. Our project is the first to propose the in vitro analysis of a series of pesticides commonly found in the environment on ALL ion channels expressed in bees. Their cloning and functional analysis will provide a unique tool to better understand the toxicity of these molecules, and build a complete picture of the synaptic sensitivity of bees to inputs. This project has several components:

  • Functional and structural characterization of ion channels and receptors in the honeybee Apis melifera
  • Toxic effects of insecticides: in vivo and in vitro studies in bees and mammals
  • Cellular transcriptomics in bees: identification of ion channels and receptors involved in excitability in various key cell types: skeletal muscle, cardiac muscle, antennal and antennal lobe neurons, Kenyon cells…
  • Identification of binding sites for these molecules in sensitive channels, in collaboration with A. Chavanieu (IBMM).
  • Search for tissue and/or species-specific toxins of these conductances to help analyze their role in vivo, and possibly provide leads for pest control. In collaboration with S. Dutertre (IBMM).

Some of the genes encoding the Cava subunits of voltage-gated calcium channels are bi-cistronic, producing both a Ca2+ ion-selective transmembrane channel protein, and a protein corresponding to the cytoplasmic C-terminal part of the channel, known as a1CT. For two of the ten genes encoding Cava subunits (Cava1.2 and Cava2.1), it has been shown that the a1CT protein (a1CCT and a1ACT, respectively) is addressed to the nucleus in several types of central nervous system neurons, where it is able to modulate the expression of certain genes involved in neurodevelopment. Its direct binding to promoter regions makes a1CT an unexpected transcription factor. Alternative splicing leads to the expression of different isoforms of a1ACT, but it is not known whether the transcriptional activity of these different splice variants is similar or not. In addition, there are interaction sites between a1ACT or a1CCT and other proteins, such as the auxiliary subunits of Cavb calcium channels. But, again, we don’t know how these interactions influence transcriptional activity. Finally, do (1) other genes encoding Cava subunits (in particular Cava2.2 and Cava2.3) produce a 1CT protein, (2) are all splice variants of these proteins expressed, (3) do these proteins have sites of interaction with Cavb, (4) are these proteins also transcription factors and, (5) is their transcriptional activity modified by alternative splicing or interaction with Cavb? Furthermore, can these calcium channel properties be extended to other voltage-dependent channels (sodium channels, etc.)? Do these properties exist in insect channels, particularly in bees?

The excitatory neurotransmission provided by glutamate is fundamental to the transmission of information in mammals. It enables rapid communication between neurons, and its plasticity is required for the brain’s adaptation to new challenges such as learning and memorizing new information. Numerous studies have shown that excitatory neurotransmission is disrupted in pathological conditions (neurodevelopmental and neurodegenerative diseases). These disturbances are concomitant with the onset of significant oxidative stress. Indeed, the accumulation of oxygenated free radicals is an aggravating factor in all cerebral pathologies. However, brain cells have antioxidant protection systems, the main one being reduced glutathione (GSH). This tripeptide (g-Glu-Cys-Gly) enables the reduction of oxidized biomolecules. Its altered metabolism is also implicated in disturbances of excitatory neurotransmission. The aim of our project is therefore to study the relationship between oxidative stress and excitatory neurotransmission in the hippocampus, by specifically examining:

  • The impact of GSH metabolism on glutamatergic synaptic activity and plasticity.
  • The role of GSH-derived glutamatergic dipeptides in mammalian cellular excitability: their targets and effects.

 

The members of the team

Pierre CHARNET

TEAM LEADER

Pierre Charnet got his PhD in 1988 on animal physiology at Tours University (France) on the regulation of cardiac Ca channels. After a Postdoc at Caltech (lab Henry Lester, Pasadena, Ca, 1988-19990) on the structure-function relationships of mammalian nicotinic acetylcholine receptors,  analyzed by expression in Xenopus oocytes…

Michel VIGNES

DEPUTY TEAM LEADER

Michel Vignes is currently Professor of Neurosciences at the University of Montpellier. Since he got his PhD, he has been working on the excitatory synaptic transmission by studying the pharmacology of both metabotropic and ionotropic glutamate receptors and by assessing their involvement in synaptic plasticity in the hippocampus…

CENS Thierry
Thierry Cens

Associate Scientist (permanent staff)

Thierry Cens obtained his PhD degree in 1997 from the University of Montpellier, France, under the supervision of Dr. Pierre Charnet, working on voltage-gated calcium channels. Then he moved, as an EMBO postdoctoral fellow, to the University of Geneva in the group of Professor Yves Dunant. In 2000, he obtained...

CHARNET Pierre
Pierre Charnet

Senior Scientist (permanent staff)

Pierre Charnet got his PhD in 1988 on animal physiology at Tours University (France) on the regulation of cardiac Ca channels. After a Postdoc at Caltech (lab Henry Lester, Pasadena, Ca, 1988-19990) on the structure-function relationships of mammalian nicotinic acetylcholine receptors,  analyzed by expression in Xenopus oocytes, he got a...

COHEN-SOLAL Catherine
Catherine Cohen-Solal

Technician (permanent staff)

Catherine Cohen-Solal obtained her baccalaureate in 1985, following which she joined the private sector as a Biology Technician at Sanofi Montpellier. Then she joined the University of Montpellier in the Functional Neuromorphology Laboratory - EPHE in 1997. Since 2004 following a competition, she has been a technician in the public...

FERREIRA Marie-Céleste
Marie-Céleste Ferreira

Assistant Professor (permanent staff)

Marie Celeste De Jesus Ferreira obtained her PhD degree (1998) from the University of Paris VI, France, under the supervision of Dr. Claire Bailly. She worked on the characterization of transduction mechanisms involved in inhibition of mouse thick ascending limb’s transport function: role of endothelin and extracellular calcium. Then, she...

GUIRAMAND Janique
Janique Guiramand

Associate Scientist (permanent staff)

Janique Guiramand is a neuropharmacologist. Following her PhD in 1991 on the characterization of the newly discovered metabotropic glutamate receptors and a post-doctoral fellow on the long and short isoforms of dopamine D2 receptors, she focused her work on the regulations of development and survival of neurons. In particular with...

MéNARD Claudine
Claudine Ménard

Assistant Professor (permanent staff)

Dr. C. Menard began her Ph.D. studies in calcium channels properties with Dr. P. Lory at the University of Sciences in Montpellier, France. After a postdoctoral position at the Harvard University, Boston, USA with Professor S.C. Cannon Dr. C. Menard has been recruited as lecturer at the University of Sciences...

ROLLAND-FULCRAND Valérie
Valérie Rolland-Fulcrand

Full Professor (permanent staff)

Valérie Rolland is Professor in chemobiology specially in aminoacids and peptide synthesis. After a PhD in enzymatic peptide synthesis and a postdoctoral position at Carlsberg Research Center in Copenhagen on the use of glutamic acid specific endopeptidase in peptide synthesis, she obtained a permanent position as assistant professor in the...

ROUSSEL Julien
Julien Roussel

Assistant Professor (permanent staff)

Dr. Julien ROUSSEL obtained his Ph.D. in 2014 from Université de Montpellier, France, for his work on carnitine effect on heart rhythm under direction of Pr. Le guennec and Dr. Fauconnier. After a postdoctoral position research in Università degli studi di Bari ALDO MORO, in Italia, on physico-chemical characterization of...

ROUSSET Matthieu
Matthieu Rousset

Associate Scientist (permanent staff)

Matthieu Rousset is a specialist in the function and modulation of voltage-gated calcium channels, which he studied during his PhD in the laboratory of Pierre Charnet in Montpellier and his postdoctoral work in the laboratory of Ricardo Dolmetsch at Stanford University. These studies were done primarily in the Xenopus oocyte...

THIBAUD Jean-Baptiste
Jean-Baptiste Thibaud

Emeritus ,Senior Scientist (permanent staff)

Jean-Baptiste THIBAUD got his PhD in May 1981 from the University of Montpellier, France under the supervision of Prof. Claude Grignon (research work dealt with chemiosmotic coupling of nitrate uptake with H+-ATPase activity in maize roots). From October 1981 he got a contractual position at the "Centre National de la...

VIGNES Michel
Michel Vignes

Full Professor (permanent staff)

Michel Vignes is currently Professor of Neurosciences at the University of Montpellier. Since he got his PhD, he has been working on the excitatory synaptic transmission by studying the pharmacology of both metabotropic and ionotropic glutamate receptors and by assessing their involvement in synaptic plasticity in the hippocampus. He has...

Team Publications