The role of post-synaptic GPCR intracellular trafficking and signalling on synaptic plasticity

Neurodegenerative disorders are among the top ten illnesses with no treatments to cure or slow disease progress. Cognitive decline observed in these conditions is linked to impaired synaptic transmission in areas of the brain involved in memory consolidation, namely the hippocampus. Synaptic plasticity in hippocampal neurons is regulated by location of receptors in cells via their trafficking. Some of these receptors, called G protein-coupled receptors (GPCRs) are able to signal from both the cell surface and intracellular compartments. Our goal is to identify the molecular mechanisms of GPCR trafficking in hippocampal neurons, its impact on signalling and the effect on synaptic plasticity. Using super-resolution microscopy combined with newly-developed probes we will develop new approaches to visualize in live cells, in real time, the trafficking and signalling of neuronal GPCRs. Uncovering the mechanisms of GPCR-mediated synaptic plasticity will contribute to the development of cures for neuropathological conditions affecting cognition and memory.