Team : CHOQUET
Impact of AMPAR dynamic nano-organization on synaptic transmission (Eric Hosy).
Project Leader(s): Eric Hosy
Contact: Eric HOSY
Tel. (+33) 5 33 51 47 30
Eric Hosy is a CNRS research director. He joined the team of Daniel Choquet in 2009 and participated to the creation of the Interdisciplinary Institute for Neuroscience and launched a new research area on using super resolution imaging approaches to study the nanoscale organization of excitatory Synapses.
This activity is headed by Eric Hosy (CR1, senior researcher) and currently involves, Hanna Zieger (Post doctoral fellow, ANR), Côme Camus (PhD student, granted by French ministry) and Diogo Soares (PhD student, granted by European ITN). The topic started when application of new high density super-resolution imaging technique reveals that AMPAR are not homogenously distributed inside the synapse but organized in nanodomains of around 80 nm which contained around 25 receptors aligned with pre-synaptic release site. Based on this discovery, the objective is to couple super-resolution imaging technique (U-PAINT, sptPALM, dSTORM) with electrophysiology and modeling to decipher how glutamate receptor organization and mobility impact on the synaptic transmission properties at the basal state, during plasticities and by some pathologies. The different topics mainly studied in the group concern:
- The development or the improvement of new high density live imaging technics
- The understanding of the molecular compounds which organize AMPAR inside the synapse
- The co-organization between AMPAR-NMDAR and mGluR
- The regulation of AMPAR dynamic organization during synaptic plasticity and pathologies (autism, mental retardation)
Trajectory and localization map of AMPA receptor inside synapse with U-PAINT (left image) and dSTORM (right image) super-resolution techniques. Analysis of such experiments revealed that AMPAR are organized in hot spot called nanodomains, containing around 25 receptors. One aim of the group is to see if there is a correlation between one nanodomain and a miniEPSC (see current traces below).
We use all the various super-resolution imaging technique on living and fixed tissue (U-PAINT, sptPALM, dSTORM, STED). Calcium imaging, electrophysiology (brain slices and neuronal cell culture), synaptic modeling
Giannone G*, Hosy E*, Levet F, Constals A, Schulze K, Sobolevsky AI, Rosconi MP, Gouaux E, Tampé R, Choquet D, Cognet L. 2010 Dynamic superresolution imaging of endogenous proteins on living cells at ultra-high density. Biophysical Journal.
Nair D*, Hosy E*, Petersen J.D, Constals A, Giannone G, Choquet D, Sibarita J-B. 2013 Super-resolution imaging reveals that AMPA Receptors inside synapses are dynamically organized in nanodomains regulated by PSD95. Journal of Neuroscience.
Pougnet J-T, Toulme E, Martinez A, Choquet D, Hosy E, Boué-Grabot E. 2014 ATP P2X receptors downregulate AMPA receptor trafficking and postsynaptic efficacy in hippocampal neurons. Neuron.
Constals A, Penn AC, Compans B, Toulmé E, Phillipat A, Marais S, Retailleau N, Hafner AS, Coussen F, Hosy E* and Choquet D*. 2015 Glutamate Induced AMPA Receptor Desensitization Increases their Mobility and Modulates Short-Term Plasticity Through Unbinding from Stargazin. Neuron.
Schneider R, Hosy E, Kohl J, Klueva J, Choquet D, Thomas U, Voigt A, Heine M. 2015 Mobility of calcium channels in the presynaptic membrane. Neuron Levet F., Hosy E, Kechkar A, Choquet D, Sibarita JB. 2015 SR-Tesseler: a novel segmentation and quantification method for localization-based super-resolution microscopy data using polygons. Nature methods.
Haas K.T., Compans B., Letellier M., Bartol T.M., Grillo-Bosch D., Sejnowski T.J., Sainlos M., Choquet D., Thoumine O., Hosy E. 2018. Pre-post synaptic alignment through neuroligin-1 tunes synaptic transmission efficiency. Elife. Jullié D., Stoeber M., Sibarita J-B., Zieger H., Bartol T., Arttamangkul S., Sejnowski T., Hosy E., von Zastrow M. 2019. A discrete presynaptic vesicle cycle for neuromodulator receptors. Neuron.
Compans B., Martineau M., Klaassen R., Bartol T., Butler C., Kechkar A., Perrais D., Sejnowski T., Sibarita J-B., Smit A., Choquet D., Hosy E. 2019. NMDAR and ATP -dependent Long-Term Depression trigger distinct molecular reshuffling, impacting differently neuronal responsiveness. BioRXiv.
Audrey Constal (PhD student) - Kalina Haas (PhD student) - Estelle Toulmé (post-doctoral fellow) - Benjamin Compans (PhD student and post-doctoral fellow) - Julia Goncalves (PhD student)
ANR AMPAT, ERC DynSynMem