TRAPAMPAR · Role of lateral diffusion of AMPA Receptors in LTP

Synaptic recruitment of AMPA receptors (AMPAR) is a critical step in synaptic plasticity events such as Long term potentiation (LTP). Although the signaling events necessary for the induction of LTP are well known (i.e. NMDA receptor activation and activation of protein kinase cascades), the source of the newly inserted AMPAR is still unclear. There are two pools of AMPA receptors that can be potentially mobilized to the synapse during LTP: a pool of AMPAR-containing intracellular vesicles and a pool of membrane-located extrasynaptic AMPAR. Since recent studies carried out mainly at the host laboratory have demonstrated that extrasynaptic AMPAR are highly mobile (sometimes moving in and out of synapses), it is possible that the increases in synaptic transmission observed during LTP might be due to the diffusional trapping of passing extrasynaptic AMPAR. During this project I will use a combination of state of the art imaging and electrophysiological approaches to test the hypothesis that mobile extrasynaptic AMPAR correspond to the most immediate source for the newly inserted AMPAR during LTP.