Antoine Triller, Institut de Biologie de l'Ecole Normale Supérieure, Inserm, France
Quantifying molecular postsynaptic receptor dynamics: insights into synapsetic function at the mesoscale
Antoine Triller is Director of Research at Inserm, Founder of the Institute of Biology of Ecole Normale Supérieure, of the Laboratory of Excellency Memolife and of the Pierre-Gilles de Genne foundation for transdisciplinary research in Biology. He has made seminal contributions to this present-day understanding for synapses, emphasizing the essential features uniquely associated with inhibitory synapses. In 1985, visualizing for the first-time receptors in the CNS, he found that they were accumulated at synapses. The receptor type being determined by the presynapse. In 2003 he made use of the Quantum Dot to label single receptors and follow them in living neurons. A new paradigm for the synapse has then emerged, abandoning the notion of a relatively stable structure in favor of a highly dynamic metastable complex, with membrane components continuously diffusing in the plane of the membrane and recycling between internal and surface compartments. This innovative view of the synapse stability and plasticity is the result of ingenious applications of powerful single molecule super-resolution microscopy combined with state-of-the-art computational analyses. He was able to derive the functional implications of his discoveries, and then to unravel unsuspected patho-physiogical processes in Alzheimer and Parkinson neurodegenerative diseases opening new routes for therapeutic strategies.
The pre- and post-synaptic molecular components are dynamic, yet long-term stabilization in the postsynaptic response are responsible for synaptic development and long-term plasticity. Unifying the concepts of local molecule turnover with structural identity and integrity is further complicated since the synapse remains sensitive to plasticity changes that bring about new stable complexes related to learning and memory. We can now quantify the number and diffusive properties of specific molecules, and statistical thermodynamics provides a framework for analyzing and quantifying molecular fluctuations providing access to not directly measurable quantities such as effective binding energies of receptors within synapses. We will discuss here the experimental and statistical advances in the analysis of molecular fluctuations of postsynaptic receptors, that lead to quantitative descriptions of synapse-specific processes underlying dynamic turnover, long-term stability and plasticity. Further, we will detail future endeavors towards an intimate description of the cellular and molecular mechanisms that contribute to the functional specificity of neuronal networks.