The neurophysiological effects of glucagon-like peptide-1 receptor agonists on neuronal activity in the lateral septum

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Glucagon-like peptide-1 (GLP-1) is an incretin which regulates blood sugar levels by modulating insulin secretion from pancreatic beta cells and as such, agonists at GLP-1 receptors (GLP-1Rs), are important treatments for type 2 diabetes. Recent research has established that GLP-1Rs are also located in brain regions associated with learning and memory. These data suggest that agonists at GLP-1 receptors may have beneficial effects for cognitive decline associated with normal ageing, as well as dementias such as Alzheimer's disease. However, the effects of this receptor system on cortical and sub-cortical synaptic circuits is not currently understood.Building on exciting preliminary data from our labs, the student will use a combination of electrophysiological (whole-cell patch clamp and multi-electrode arrays) and behavioural approaches to examine the effect of GLP-1 receptor activation at a neuronal circuit level. During the course of this project, the student can also expect to make use of Glp1r-Cre transgenic mice which will allow us to carry out targeted circuit mapping and in vivo experiments, using opto- and/or chemo-genetic approaches.The student will gain extensive experience in brain slice electrophysiology, advanced computational analysis, in vivo recovery surgery and behavioural neuroscience. Furthermore, during the course of the project, the student will enjoy a placement (3-6 months) with our industrial partners at Eli Lilly. This combination of experience with these cutting-edge, sought-after technologies and interaction with Eli Lilly will provide an excellent foundation for a future career in academia or industrial science.The studentship will be part of the wider GERAS Collaborative Training Partnership, a BBSRC-funded Collaborative Training Partnership (CTP) between the Eli Lilly and Company Ltd, Exeter University and King's College London. Between 2017 and 2023, the CTP will deliver 11 four-year studentships in priority areas of Bioscience for health, World class underpinning bioscience, and Exploiting new ways of working. The research area of GERAS is focused on the biological basis of lifespan and healthy ageing, particularly ageing and the brain. The primary objective is the data-driven generation of new knowledge on the development and maintenance of health across the life course with the long-term objective of promoting health in later life. The training focus of the CTP is on the skills needed to understand complex biological systems from a data perspective, with core training in Bioinformatics, Programming and Coding, Statistics, and Data Science alongside professional skills training. The CTP will provide PhD students with a first-rate, challenging research training experience within the context of mutually beneficial research collaborations.