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Antoine Triller

Cellular biology of the synapse


Neurons efficiently detect, integrate and transmit information through specialization of their plasma membrane into sub-domains such as the active zone or the post-synaptic membrane, with specific properties and morphology. The efficiency and accuracy of neurotransmission strongly depends on two apparently antagonist properties of synaptic membrane: the stability of its organization and its ability to adapt to plasticity events.

In addition, the structural stability of synapses has to be reconciled with the notion that cell membranes are fluid. Membrane molecules are compelled to move within the membrane surface due to thermal Brownian agitation, which favors the homogeneous distribution of the molecules. As a result, neurons spend energy to stop or reduce these movements, and maintain molecules in certain locations via mechanisms that decrease this fluidity. Our team investigates the regulation of synaptic receptors dynamics by the different (structural and functional) elements that make the synapse.

Main findings

These last ten years, we have approached these conceptual paradoxes by developing new technological and analytical tools that allow the monitoring of the behavior of synaptic components at the molecular level and change of the scale of analysis. More precisely, we have pioneered the development of nanocrystal-based (quantum dots) single particle tracking and analysis. We demonstrated rapid exchanges between synaptic and extra-synaptic receptors and we showed that transient stabilization of receptors at synapses occurs by interaction with partners, such as scaffold proteins. Novel super-resolution imaging methods (PALM, STORM) gave us a precise insight on the organization of these postsynaptic structures. Thus, the regulations of receptor-scaffold and scaffold–scaffold interactions appear as a central tenet for the maintenance and plasticity-related changes of receptor numbers at synapses.

Fossati M, Pizzarelli R, Schmidt ER, Kupferman JV, Stroebel D, Polleux F, Charrier C (2016) SRGAP2 and Its Human-Specific Paralog Co-Regulate the Development of Excitatory and Inhibitory Synapses. Neuron 91:356-69

Cantaut-Belarif Y, Antri M, Pizzarelli R, Colasse S, Vaccari I, Soares S, Renner M, Dallel R, Triller A*, Bessis B* (2017) Microglia control the glycinergic but not the GABAergic synapses via prostaglandin E2 in the spinal cord J Cell Biol 216:2979-2989

Shrivastava AN, Aperia A, Melki R, Triller A (2017) Physico-Pathologic Mechanisms involved in Neurodegeneration: Misfolded Proteins-Plasma Membrane Interactions. Neuron 95(1):33-50 ; doi: 10.1016

Shrivastava AN, Redeker V, Fritz N, Pieri L, Almeida LG, Spolidoro M, Liebmann T, Bousset L, Renner M, Léna C, Aperia A, Melki R, Triller A (2015) α-synuclein assemblies sequester neuronal a3-Na+/K+-ATPase and impair Na+ gradient. EMBO J 34:2408-23

Specht CG, Izeddin I, Rodriguez PC, El Beheiry M, Rostaing P, Darzacq X, Dahan M, Triller A (2013) Quantitative nanoscopy of inhibitory synapses: counting gephyrin molecules and receptor binding sites. Neuron 79:308-321