Towards high spatio-temporal control of endogenous AMPA receptors short and long term synaptic plasticity – OptoXL

The dynamic regulation of AMPA receptors (AMPARs) nanoscale organization, a glutamate receptor that mediates most fast excitatory synaptic transmission in the mammalian central nervous system, constitutes a major mechanism underlying synaptic plasticity, a fundamental basis of learning and memory. We have shown recently that the surface mobility of postsynaptic AMPARs tunes frequency dependent synaptic transmission, a new mechanism to regulate short term plasticity. In parallel preliminary data from our lab and published work indicate that surface trafficking of AMPARs might also be critically involved in long-term forms of synaptic plasticity.
In this project, we want to develop innovative methods that will address current technical limitations and allow us to investigate with a unique spatiotemporal resolution the impact of AMPARs mobility in short and long terms plasticity in the brain function. More precisely, we want to design tools that will provide us with a control of endogenous or genetically modified AMPARs mobility by way of light-controlled crosslinking. By combining the expertise of our two groups, we will develop and apply these innovative tools in vivo to investigate the relation between AMPA receptor surface trafficking, synaptic plasticity at various timescales and behavior.