Sabine Levi - The dynamic synapse

We are investigating the activity-dependent cellular and molecular mechanisms that are involved in the establishment and pruning of synapses during development and those that regulate the plasticity of mature synapses. Our main model is the inhibitory GABAergic synapse in the hippocampus.
We go from the molecule to animal behavior. First, we are identifying and characterizing the cellular and molecular mechanisms in primary cultures of rat hippocampal neurons using pharmacological and genetic approaches, videomicroscopy and single-molecule imaging (Quantum Dot-based Single Particle Tracking QD-SPT and super-resolution STORM/PALM nanoscopy). This enable us to study the membrane dynamics and organization of the key players in the synapse at the nanometric scale. The functional impact of the mechanisms identified is then tested using calcium and chlorine imaging. The mechanisms of interest are further evaluated in vivo using approaches to suppress or overexpress the proteins of interest (using pharmacology, stereotaxic injection of viruses, mouse lines) on synapses and neuroglial interactions using 3D imaging and image analysis on Metamorph and Imaris, as well as on animal behavior (memory, social interactions, anxiety, epilepsy, etc.).
By combining powerful genetic tools with the simple nervous system of C. elegans, Marie Gendrel, who leads a small group in the laboratory, is seeking to identify and characterize new presynaptic determinants of GABAergic transmission, focusing mainly on putative and known amino acid transporters in C. elegans. Unlike vertebrates, most of the worm’s transporters have not been characterized. Once identified, their vertebrate orthologs will be tested for GABA transport, as already known components of the GABAergic machinery are highly conserved between mammals and worms.