Joana Ferreira and Thomas Papouin ineLife

Co-agonists differentially tune GluN2B-NMDA receptor trafficking at hippocampal synapses. Ferreira JS, Papouin T, Ladépêche L, Yao A, Langlais VC, Bouchet D, Dulong J, Mothet JP, Sacchi S, Pollegioni L, Paoletti P, Oliet SHR, Groc L. Elife. 2017 Jun 9;6. pii: e25492. doi: 10.7554/eLife.25492.

Laurent Groc: Interdisciplinary Institute for NeuroSciences, CNRS , Bordeaux, France
Stéphane Oliet:  Neurocentre Magendie, Inserm, Bordeaux, France

NMDA receptors are part of a family of glutamate receptors, which play a crucial role in cognitive functions such as learning and memory. Studying how they traffic to synapses in various conditions has thus been a key challenge in neuroscience. In addition, a dysregulation of the NMDA receptor signaling is likely involved in the etiology of neuropsychiatric diseases, such as schizophrenia. Here, Joana Ferreira and Thomas Papouin, from Laurent Groc (CNRS IINS) and Stéphane Oliet (INSERM Neurocentre Magendie) labs, combined their efforts to demonstrate that NMDAR co-agonists, glycine and D-serine, are not only important for receptor activation, and therefore for ionotropic function, but also for the regulation of its diffusion properties and synaptic localization over time.

They used a combination of techniques from single-particle tracking in rat hippocampal cultures, biochemistry, fluorescent lifetime microscopy to electrophysiology in acute slices, to unveil this mechanism. Remarkably, they showed that this process contributes to the change in the composition of synaptic NMDARs that occurs during development, a well-known feature of glutamatergic synapses that is central to neuronal network maturation. Since blocking the receptors has been proven to be therapeutically ineffective, altering co-agonist levels may be a viable alternative to regulate the NMDA receptors in severe psychiatric disorders. But that is another story!

First authors

Joana S. Ferreira: IINS / postdoctoral fellow in Laurent Groc Team / I came to Bordeaux after concluding my PhD in Neurosciences in Coimbra, Portugal.

Thomas Papouin: Research Assistant Professor at Tufts University school of Medicine, Boston (USA). Thesis under supervision (2011) of Stéphane Oliet in his team “Glia-neuron relations” at Bordeaux Neurocampus