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 (UNIS) is composed of three research groups whose main objective is to understand the molecular mechanisms of neurotransmission and the role of ion channels in neuronal communication, plasticity and brain diseases.

Our approach goes from the molecular study of ion channels and synaptic proteins (using molecular biology and biochemistry techniques) to the functional study (using electrophysiology and cell imaging), but also includes the investigation of the expression patterns of ion channels and of their interaction with cellular proteins (using cell cultures and immunohistochemistry).

The changes in function of ion channels and synaptic proteins involved in physiological plasticity (Hebbian and homeostatic plasticity) or pathological plasticity (epilepsy models, sensory deprivation) are also studied in our laboratory.

The laboratory also has a technological platform, which aims to develop novel molecular tools for the diagnosis and prognosis of neurological disease.

We use a wide range of experimental techniques: biochemistry, cell and molecular biology, confocal imaging, functional imaging   and electrophysiology.

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 mainly interested in the molecular mechanisms of neurotransmitter release and its calcium sensitivity.
A maturation process prepares loaded synaptic vesicles approaching the plasma membrane in order to prepare them for fusion. This maturation involves primarily the assembly of protein complexes at the interface between the compartments destined to fuse. A set of specialized SNARE (Soluble N-ethylmaleimide-sensitive-factor Attachment protein REceptor) proteins is believed to be the minimal fusion machinery.
The precise mechanism by which membrane fusion is executed is still a fuzzy area. It initially involves formation of a fusion pore, a channel–like structure crossing synaptic vesicle and plasma membranes, thus allowing the synaptic vesicle contents to escape. Several molecular partners such as the V-ATPase (vacuolar proton ATPase) interact with SNARE proteins and modulate neurotransmitter release. V-ATPase is a giant multi-molecular nano-motor present in all eukaryotic cells. The primary function of V-ATPase is proton pumping. Independent from its proton transport activity, the V0 membrane sector of the V-ATPase interacts with SNARE proteins and interferes with SNARE-mediated exocytosis. We are also interested in developing highly sensitive in vitro assays to detect the proteolytic activity on SNARE proteins of botulinum neurotoxins (BoNT) as well as in studying BoNT receptors.

Members

EL FAR Oussama, BAUDOUX-SANGIARDI Marion, DESPLANTES Richard, FORMISANO-TREZINY Christine, GABERT Jean, IBORRA-BONNAURE Cécile, LEVEQUE Christian, MAULET Yves , MOUTOT Nicole , SEAGAR Michael, YOUSSOUF Fahamoe. Total : 5 HDRs.

Research axes

Our projects focus on the following two aspects:

  • The functional implications of V0 V-ATPase coupling to SNAREs in controlling neurotransmitter release.
  • Receptors of Botulinum neurotoxins and activity detection assays.

Techniques

  • Molecular biology
  • Biochemistry
  • Cell culture
  • Immunostaining, histology
  • Microscopy
  • Electrophysiology (on slices or cells)
  • Bioinformatics

Keywords

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

Excitability, synaptic transmission, network functions

Dynamics of neuronal excitability (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, ANKRI Norbert, BOUMEDINE Norah, CAILLARD Olivier, FEKETE Aurélie, FRONZAROLI-MOLINIERES Laure, INGLEBERT Yanis, RAMA Sylvain, RUSSIER Michaël, ZANIN Emilie, ZBILI Mickaël. Total : 2 HDRs.

Research axes

  • Plasticity of intrinsic neuronal excitability
  • Determinants of neuronal timing
  • Axon function

Techniques

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

Keywords

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

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

Homeostasis of excitability and neuromodulation (Jean-Marc Goaillard)

Our work focuses on the molecular mechanisms underlying the robustness of neuronal activity. The properties of ion channels or synapses are dynamically regulated to maintain a stable level of activity, despite numerous external or internal disturbances. This stability depends on the dynamic regulation of various ion channels responsible for neuronal activity. We believe that dynamic processes regulate in a coordinated manner the properties of functionally-overlapping ion channels. We seek to determine the mechanisms responsible for the dynamic regulation of ion channels in the dopaminergic neurons of the substantia nigra pars compacta of rodents. These neurons are able to spontaneously generate regular activity patterns in the absence of any stimuli (including synaptic inputs). This “pacemaker” property allows us to precisely define their patterns of activity in vitro and to determine the causal relationships between the properties of the voltage-gated ion channels expressed by these neurons and their physiological output. The work requires measuring properties or expression levels of several ion channels in the same cells to identify any co-variation in their properties.

Members

GOAILLARD Jean-Marc, BAUDOT Pierre, HADDJERI-HOPKINS Alexis, LASSERRE Manon, MARQUÈZE-POUEY Béatrice, MOUBARAK Estelle, TAPIA-PACHECO Mónica. Total : 1 HDR.

Research axes

  • Define the regulation of conductances (at the level of gene expression but also at the level of biophysical properties) induced by internal (ion channel KO) or external (pharmacological manipulations) perturbations of dopaminergic neuron activity.
  • Determine the functional impact of conductance coregulation (long- and short-term) on neuronal activity (tuning of activity or homeostasis) using computational techniques
  • Define the link between robustness of neuronal activity and information coding optimization

Techniques

  • Molecular biology
  • Biochemistry
  • Cell culture
  • Immunostaining, histology, or flow cytometry
  • Microscopy
  • Electrophysiology (on slices or cells)
  • Bioinformatics

Keywords

Robustness, plasticity, electrophysiology, ion channels, substantia nigra pars compacta, dopamine

Excitability, synaptic transmission, network functions - Motor systems
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