The integrity of rapid signaling between neurons at central excitatory synapses critically depends on AMPA-type glutamate receptor ion channels (AMPARs). AMPARs are enriched at postsynaptic sites, where they bind the neurotransmitter glutamate and depolarize the postsynaptic neuron, thereby relaying information from one neuron to the next. Activity-dependent recruitment of additional AMPARs is widely thought to underlie persistent strengthening ('potentiation') of synapses during early stages of memory formation in the hippocampus.

We have recently shown that there are distinct contributions of various AMPA receptor trafficking routes to the temporal profile of synaptic potentiation (Penn et al. 2017, Nature, In Press). In this model, AMPARs diffusing passively on the membrane surface become trapped temporarily at the postsynaptic density immediately following high-intensity synaptic activity. These receptors are then gradually replenished by AMPARs delivered from intracellular stores by a sequence of trafficking steps involving membrane fusion and surface diffusion. Together, these AMPAR trafficking mechanisms contribute to stable, long-lasting synaptic potentiation.

The findings imply that the stabilization of AMPARs captured by diffusional trapping is short-lived. The aim of this PhD is to understand what regulates the different trafficking routes of the AMPAR. In particular, the project will focus on addressing the question of why the initial activity-dependent stabilization of AMPARs is so labile.

We are currently funded by the Medical Research Council and have resources and expertise to use a multidisciplinary research approach including molecular biology, organotypic slice culture, cell culture and patch-clamp electrophysiology. Our lab collaborates with Professor Simon Ward at the Sussex Drug Discovery Center (SDDC), who is developing new drugs targeting AMPA receptors with the aim of improving cognitive performance (http://www.sussex.ac.uk/broadcast/read/25715). The Penn lab is housed in well-resourced laboratory spaces within Sussex Neuroscience (http://www.sussex.ac.uk/sussexneuroscience/). The PhD studentship is funded by the School of Life Sciences at the University of Sussex.