Annie Andrieux, Fabio Benfenati, Gerard Borst, Jamel Chelly, Lydia Danglot, Frédéric Darios, Pietro De Camilli, Thierry Galli, Frédéric Gambino, Etienne Herzog, Yann Humeau, Philippe Isope, David Perrais, Maja Petkovic, Bernard Poulain, Jakob B. Sorensen, David Tareste, Matthijs Verhage
by Thierry Galli and Yann Humeau
24 – 29 September , 2012
Keywords: Synapse, Neurotransmitter release, Synaptic Plasticity, Intellectual Disability
The seminar entitled « Presynapse: function, plasticity, dysregulations » brought together experts working on functional and molecular presynaptic mechanisms, which are essential for neuronal communication. The purpose of the discussions was to understand the role played by the absence of important presynaptic factors in a wide range of nervous pathologies, including severe forms of epilepsy, schizophrenia, syndromic and non-syndromic cognitive deficits and familial migraines. Among the new concepts discussed during this seminar, we noted the emergence of fusogenic lipids as major players in the regulation of presynapses, their study becoming facilitated by the introduction of new optogenetic tools. Functional studies also helped to highlight the presence of vesicular pools in addition to those usually described for the fine tuning of synaptic efficacy during episodes of high frequency neuronal activity. From pathophysiological studies, it appeared fairly obvious that the presynapses are functional sites affected by genetic mutations associated with mental disturbances. In this respect, the role of many actors such as microtubules, monomeric G proteins, phosphoproteins and trans-synaptic signaling proteins was described. Interestingly, many large-scale programs characterizing these changes are underway, including examination of the co-responsibility of large networks of genes as a cause of cognitive disorders. Indeed, the accumulation of “weak” alleles combined with the appearance of a stochastic combination of mutations could explain the emergence of synaptic pathologies including genetic ones which are not strictly monogenic or polygenic. In a final round table, the importance of complementarity of research on large gene networks and systematic research on specific genes as well as the emergence of new methodological tools for the study of presynapses were addressed.
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