UNIS - INSERM U 1072

Ion Channel and Synaptic Neurobiology

Director : Dominique DEBANNE

Faculté de Médecine Nord
51 Bd Pierre Dramard
13916 Marseille CEDEX 20
France

The Ion Channel and Synaptic Neurobiology Laboratory or UNIS (INSERM – Aix-Marseille University, UMR 1072) is focused on the role of ion channels in neuronal signaling, plasticity and diseases of the nervous system.

Group 1 (O. El Far) is studying the molecular mechanisms of neurotransmitter release and intrinsic excitability. Three project are tackled by the group: 1) synaptic transmission modulation by subunits of the vesicular V-ATPase, 2) control of neuronal excitability by the protein LGI1 and 3) activity and receptors of botulinum neurotoxins.

Group 2 (D. Debanne) is aiming at understanding the mechanisms of induction and expression of the plasticity of intrinsic excitability in central neurons as well as axon physiology.

Group 3 (J.M. Goaillard) is analyzing the molecular and cellular mechanisms that underlie the robustness of neuronal firing in the substantia nigra.

Group 4 (P. Marcaggi) focuses on the mechanisms of cerebellar plasticity in relation to behavior.

Pictures from the UNIS laboratory

The research teams

All UNIS teams are affiliated to the neuroscience master’s program and can thus train neuroscience master’s students and offer them projects to apply for a Ph.D. scholarship.

Molecular mechanisms of neurotransmitter release (Oussama El Far)

We are interested in 3 parallel research axes:

1-We are particularly interested in the implication of the V-ATPase subunits “V0c” and “V0d” in the modulation of neurotransmitter release.

2-We are interested in studying the effect of LGI1 and its autoantibodies on the regulation of Kv1 channel expression and the consequences on neuronal excitability and synaptic transmission.

3-Through cellular biology, biochemistry and modeling approaches we aim at deciphering the molecular mechanisms that govern the recognition of botulinum neurotoxins by their neuronal receptors.

Members

EL FAR Oussama, MAULET Yves, FANTINI Jacques, YAHI Nouara, CHAHINIAN Henri, LEVEQUE Christian, RAMIREZ-FRANCO Jose-Jorge, SEAGAR Michael, BAUDOUX-SANGIARDI Marion, YOUSSOUF Fahamoe, FLORES Alessandra. Total : 4 HDRs.

Research axes

  • Synaptic transmission modulation by subunits of the vesicular V-ATPase
  • Control of neuronal excitability by the protein LGI1 (Leucine-rich Glioma-Inactivated 1)
  • Activity and Receptors of Botulinum Neurotoxins

Techniques

  • Molecular biology
  •  Biochemistry
  •  Cell culture
  •  Immunostaining, histology, flow cytometry
  •  Microscopy
  • Pharmacology

Keywords

Synapse, membrane fusion, exocytosis, synaptic vesicles, neurotransmitter release, protein complexes, Botulinum neurotoxins

Excitability, synaptic transmission, network functions - Novel methods and technology development

Dynamics of neuronal excitability and epilepsy (Dominique Debanne)

A large part of our research activity is devoted to characterizing interactions between synaptic and intrinsic plasticity. We established that learning rules defined for synaptic transmission are valid for plasticity of dendritic integration in CA1 pyramidal neurons. We demonstrated that GABAergic interneurons also express plasticity of intrinsic excitability. We are exploring i) the activity-dependent regulation of Kv1 channels, ii) the mechanisms underlying intrinsic plasticity induced in parallel with synaptic long-term depression and iii) the role of intrinsic plasticity in amblyopia.

We are also exploring the factors determining neuronal synchronization at two strategic points: the synapse and the axon initial segment. We established that the synaptic delay depends on release probability and presynaptic spike waveform. Thus, synaptic delay is modified during several forms of short- and long-term synaptic plasticity.
We also demonstrated the role of voltage trajectories preceding the spike in temporal precision of spike firing. We also explore the role of inhibitory synaptic activity in the precision of neuronal discharge.

Finally, our work also examines how voltage-gated ion channels in the axon determine information processing in hippocampal and neocortical circuits. We aim to determine the axonal mechanisms of analog-digital modification of synaptic strength.

Members

DEBANNE Dominique, Michael Russier, Norbert Ankri, Laure Molinieres, Norah Boumedine, Yanis Inglebert, Aurélie Fékété. Total : 2 HDRs.

Research axes

  • Intrinsic plasticity
  • Synaptic plasticity in the hippocampus
  • Axon physiology

Techniques

  • Molecular biology
  • Cell culture
  •  Immunostaining, histology, flow cytometry
  •  Microscopy
  •  Calcium imaging
  •  Electrophysiology (on slices or cells)
  • Animal surgery, stereotaxy
  •  Pharmacology
  • Modeling

Keywords

Synaptic plasticity, initial segment, intrinsic plasticity, time, synaptic transmission, ion channels, hippocampus, cortex, amblyopia

Computational neuroscience - Disorders of the nervous system - Excitability, synaptic transmission, network functions - Sensory systems

Robustness of excitability (Jean-Marc Goaillard)

Our work focuses on the molecular mechanisms underlying the robustness of neuronal activity. A number of studies have demonstrated that neurons are able to maintain stable pattens of activity in spite of the numerous internal and external perturbations they are constantly submitted to. Pharmacological manipulation or sensory deprivation experiments have shown that synaptic and ion channel properties are dynamically regulated in order to maintain a stable level of activity (for review see Turrigiano, Cell, 2008). Moreover, a growing number of studies have demonstrated that the chronic deletion of ion channels (KO animals) might only slightly alter neuronal activity (see for instance Swensen & Bean, J. Neurosci. 2005), illustrating the ability of neurons to compensate for the random mutations that spontaneously occur in the genome. It seems rather obvious that this stability depends on the dynamic regulation of the numerous ion channel subtypes (ligand-gated or voltage-gated) responsible for neuronal activity.

Members

GOAILLARD Jean-Marc, Fabien Tell, Béatrice Marquèze-Pouey, Jean Gabert, Christine Formisano-Tréziny, Monica Tapia, Pierre Baudot, Estelle Moubarak, Alexis Hadjjeri-Hopkins. Total : 3 HDRs.

Research axes

  • Robustness of pacemaking to biophysical variability
  • Transcriptome to phenotype mapping

Techniques

  • Molecular biology (PCR…)
  •  Biochemistry (Western blot…)
  •  Cell culture
  •  Immunostaining, histology, flow cytometry
  •  Microscopy
  • Pharmacology
  • Bioinformatics

Keywords

Homeostatic plasticity, robustness, ion channels, electrophysiology, transgenic animals, single-cell transcriptomics.

Computational neuroscience - Development of the nervous system - Disorders of the nervous system - Excitability, synaptic transmission, network functions

Excitatory transmission and plasticity mechanisms in the cerebellar cortex (Paikan Marcaggi)

In humans and rodents, the majority of neurons are found in the cerebellum where the most abundant synapses are the excitatory granule cell to Purkinje cell synapses. In vitro studies in rodents have demonstrated that the strength of transmission at these synapses can be modified by plasticity mechanisms, various ones. Some of them may underlie information storage, while others may reflect homeostatic processes. One of our goals is to link synaptic plasticity mechanisms to specific functions.

We have studied the roles of two G-protein coupled receptors involved in synaptic plasticity mechanisms : type 1 metabotropic glutamate receptors and type 1 cannabinoid receptors. Now, we propose new experimental approaches based on the use of optogenetic tools, micro-technology and calcium imaging to better understand the cellular interactions that take place at the granule cell to Purkinje cell synapse. In parallel, we investigate quantitatively the distribution of synaptic strengths, which appears to be highly heterogeneous. We aim to test whether this heterogeneous distribution is a memory trace and whether it correlates with the amount of cerebellar learning.

Members

Païkan Marcaggi, Shu Ho. Total : 1 HDR.

Research axes

  • Synaptic strength distribution and cerebellar learning
  • Signaling at the central excitatory synapse

Techniques

  • Immunostaining, histology, flow cytometry
  •  Microscopy
  •  Calcium imaging
  •  Electrophysiology (on slices or cells)
  • Pharmacology
  •  Animal behavior
  • Optogenetics

Key words

Synapse, plasticity, cerebellum, glutamate, metabotropic glutamate receptors, calcium signaling, endocannabinoids, memory trace, metabolism, transporters.

Animal cognition and behavior - Development of the nervous system - Excitability, synaptic transmission, network functions - Motor systems - Novel methods and technology development - Sensory systems
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