Regulation of glutamate receptors during synaptic plasticity (2017)

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.

Type of award

Postgraduate Research

Award amount

The award covers Home/EU fees, a stipend of £14,553 pa and research and training allowance

Eligibility

Applicants are expected to hold a 1st class of 2.1 degree or equivalent in Neuroscience or a relevant subject.

Only full time UK or EU students will be accepted.

Application procedure

To be considered complete online application http://www.sussex.ac.uk/study/phd/apply

Apply for PhD in Neuroscience, February 2018 start (2017-18 entry). Mention name of supervisor in "suggested supervisor" section. In funding mention sponsored or seeking funding. In Award details mention School of Life Sciences funded studentship. Include brief statement of interest (upto 2 pages), CV, two academic references, UG/PG transcripts, IELTS results if residing in EU. The studentship is for 3.5 years (full fee waiver, stipend Research Council equivalent rate).

Only full time UK or EU students will be accepted.

Timetable

Deadline to apply is Sunday, 10th December 2017.

Contact details

For informal enquiries contact Dr Andrew Penn (A.C.Penn@sussex.ac.uk)

For application enquiries contact Anna Izykowska (A.Izykowska@sussex.ac.uk)

Availability

Available to:
UK, Europe (Non-UK)

At level(s):
PG (research)

Application deadline:
10 December 2017