HDR : Nanoscale AMPA receptor organization and synaptic transmission properties
March 25, 2016
Historically, scientific progress is intrinsically linked to technological and methodological advances. In biology, the development of each new technique has uncovered a new vision and therefore a better understanding of the organization of life. For this reason and throughout my career, I have tried to be equally involved in the development or acquisition of new methodologies and their applications in order to answer to my questions about biology. During my thesis, I adapted the techniques of electrophysiology on small plant cells (guard cells, 5 µm in diameter), and have developed the first heterologous plant system. My first post-doctoral work at the CEA in Grenoble was based on hijacking a partial inhibitor of KATP channels to re-examine the conformational changes responsible for the sensitivity of this channel to nucleotides. Finally, in the laboratory of Daniel Choquet, I developed, in collaboration with Gregory Giannone and Laurent Cognet, the only high-density super-resolution technique capable of revealing the organization of endogenous proteins in living cells. The development of these techniques allowed me to address issues that were not accessible with existing techniques, such as to re-examine the synaptic transmission properties at the nanoscale.
My future research program will continue to focus on the understanding of the physiological mechanisms underlying synaptic transmission. They represent a major challenge in neurobiology because they are responsible for the treatment and storage of information in the brain. Their understanding requires collating data on spatial (organization of proteins) and functional (channel activity) organization. This step will therefore require experiments based on the parallel use of advanced imaging techniques coupled with recording synaptic currents. This will enable synaptic function to be understood not as one of the multiple inputs of a neuron, but as an individual entity with its own dynamics and regulations. This determination of the functioning of a single synapse at the molecular level and its impact in the activity of the global network will be a key for understanding some brain diseases.
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