The Multidimensional Brain

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Pharmacology & Biochemistry of the Synapse

Group leader : Hervé Daniel
33 1 69 15 63 27

Gestionnaire :Angélique Nicolas

Despite its simple circuitry, the cerebellum appears to be a sophisticated signal processing structure in the brain and an important site of motor learning. In the cerebellar cortex Purkinje cells, the sole output neurons, receive glutamatergic inputs from parallel and climbing fibers. These neurons are closely associated with Bergmann glial cells that surround both somata and synapses in a glial sheath.
Our team have two main research objectives :

1) Regulation of glutamatergic synaptic transmission by presynaptic metabotropic receptors.
(Electrophysiological approaches: Heather McLean; molecular approaches Catherine Berrier)

In the first study, we focus on presynaptic control of glutamate release by the metabotropic glutamate receptor, mGluR4. This receptor is an exciting target for the development of new therapeutic agents in the treatment of certain neurological disorders. We are particularly interested in understanding the molecular and cellular signalling pathways of these receptors. More specifically, we are looking to identify their protein partners and how they are involved in the negative regulation of glutamate release.
Based on our long-standing experience in the study of synaptic transmission and plasticity, we have adopted a strategy combining complementary electrophysiological, pharmacological and molecular approaches in order to study and compare recombinant and native mGluR4 receptors.

2) Neuron-glia interactions. (Micaela Galante)

The second objective is to investigate the role of Bergmann glia in [K+]e and water homeostasis in both physiological and pathological conditions. We are currently using ion-sensitive microelectrodes to record changes in [K+]e and in extracellular volume associated with Purkinje cell activity while simultaneously recording Bergmann glia. Electrophysiological and calcium imaging techniques are associated to optogenetics to study this topic..

Techniques:
- Patch clamp and presynaptic/postsynaptic Ca2+ imaging on acute cerebellar slices
- Ion-sensitive microelectrodes
- Optogenetic tools
- Innovative pharmacological tools
- Expression (bacteria, yeast and a-cellular systems) and purification of membrane proteins
- Biochimical methods to characterize protein-protein interactions (Co-immunoprecipitation, Affinity and Exclusion Chromatography, spectrofluorescence…)
- Proximity Ligation Assay (PLA).


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