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

胰高血糖素样肽-1 （GLP-1）是一种肠促胰岛素，通过调节胰腺细胞的胰岛素分泌来调节血糖水平，因此，GLP-1受体的激动剂（GLP-1Rs）是2型糖尿病的重要治疗方法。最近的研究已经证实，GLP-1Rs也位于与学习和记忆相关的大脑区域。这些数据表明，GLP-1受体的激动剂可能对与正常衰老相关的认知能力下降以及阿尔茨海默病等痴呆症有有益的影响。然而，这种受体系统对皮层和皮层下突触回路的影响目前尚不清楚。基于我们实验室令人兴奋的初步数据，学生将使用电生理学（全细胞膜片钳和多电极阵列）和行为方法的组合来检查GLP-1受体激活在神经元回路水平上的影响。在这个项目的过程中，学生也可以期望使用Glp1r-Cre转基因小鼠，这将使我们能够使用光和/或化学遗传方法进行靶向电路绘图和体内实验。学生将在脑切片电生理学、高级计算分析、体内恢复手术和行为神经科学方面获得丰富的经验。此外，在项目过程中，学生将与我们的工业合作伙伴Eli Lilly一起实习（3-6个月）。这种与这些前沿、受欢迎的技术的结合以及与礼来公司的互动将为未来在学术界或工业科学领域的职业生涯提供良好的基础。该奖学金将成为更广泛的GERAS合作培训伙伴关系的一部分，这是由bbsrc资助的礼来公司有限公司、埃克塞特大学和伦敦国王学院之间的合作培训伙伴关系（CTP）。在2017年至2023年期间，CTP将在生物科学促进健康、世界级基础生物科学和探索新的工作方式等优先领域提供11名四年制学生。GERAS的研究领域集中在寿命和健康老龄化的生物学基础上，特别是老龄化和大脑。主要目标是在数据驱动下产生关于在整个生命过程中发展和维持健康的新知识，其长期目标是促进晚年健康。CTP的培训重点是从数据角度理解复杂生物系统所需的技能，核心培训包括生物信息学、编程和编码、统计学和数据科学以及专业技能培训。CTP将在互惠互利的研究合作的背景下，为博士生提供一流的、具有挑战性的研究培训经验。

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.