Prize Lectures PL01 The perils and pleasures of educating 21st century physiology undergraduates J. Choate Department of Physiology, Monash University, Melbourne, VIC, Australia Over the past 10 years, many Australian universities have experienced increased student enrolments in Physiology subjects. Reasons for this increase are twofold. Firstly, changes in government funding to universities with the uncapping of student enrolments in undergraduate degree-programs provided financial incen- tives for Physiology Departments to increase their student numbers. Secondly, the funding of graduate medical degree programs in favour of undergraduate medical programs and the inclusion of Physiology as a prerequisite subject for these grad- uate medical degree programs and other allied health degree-programs provided a market for physiology graduates, and therefore a strong incentive for students to study Physiology (Choate & Long, 2019). At Monash University, student enrolments in a foundational physiology subject increased from 150 in 2011 to 720 in 2019. This increase had significant conse- quences for the Physiology academics involved in teaching. Staff had to recon- sider how to effectively deliver the Physiology curriculum to large student cohorts. Key changes included the development of virtual experiments and large-scale workshops. The virtual experiments supported, and in some cases replaced, live experimental practical laboratory classes. Analysis of student learning showed that the virtual experiments enhanced student understanding of the physiology concepts underlying the practical classes, and supported the development of research skills (Quiroja & Choate, 2017; Quiroja & Price, 2016). The introduction of large-scale workshops arose as a consequence of falling attendance at lectures. Video-recording and live streaming of lectures provided students with the option of studying lecture materials at a time and place of their own choosing. In response to the large decreases in lecture attendance, the number of lectures was reduced, or they were removed altogether. Lectures were replaced with large-scale active learning workshops (for up to 150 students) in a new Learning and Teaching Building designed for this purpose. Attendance and participation of students in these workshops has been significantly higher than lectures, which was not surprising, as the workshops were not recorded or live-streamed. To date there has been no significant impact of these workshops on student learning as measured by assessment performance. The workshops are, however, less cost-effective than lectures as they require a substantially higher staff to student ratio, necessitating the recruitment and training of additional teaching associates. With large numbers of students studying Physiology in non-vocational undergrad- uate degree programs (i.e. Science, Biomedical Science), there has been a high level of student stress and anxiety about career options. This observation, and the recent government concern about graduates’ employability skills, prompted 1P Prize Lectures the introduction of careers education into the curriculum of the Biomedical Science degree-program (Choate, Green, Cran, Macaulay & Etheve, 2016; Choate & Long, 2019). An integrated team of careers educators and biomedical science academics designed and embedded a course-wide, assessable Career Develop- ment Program into the biomedical science curriculum. This program was found to improve students’ awareness of careers options, enhance their careers confi- dence and increase their engagement with the University Careers Service (Choate et al., 2016). Importantly, the program enabled careers education on a large scale. Following this success, a new work integrated subject, involving industry-based placements, has been implemented and has further enhanced students’ career awareness. In summary, this education research highlights how a holistic approach to the student experience in physiology through on-line virtual experiments, hands-on active learning workshops and careers education can enhance student engage- ment and learning in large student cohorts. Choate J, Green J, Cran S, Macaulay J, Etheve M (2016). Using a course wide professional development program to enhance undergraduate career development and employability. International Journal of Innovation in Science and Mathematics Education. 24(3):49-70. Choate J, Long H (2019). Why Do Science Students Study Physiology? Career Priorities of 21st Century Physiology Undergraduates. HAPS-Educator, Journal of the Human Anatomy and Physiology Society. 23(1). Quiroga M, Choate J (2017). Using an online simulation to prepare students for an enquiry-based laboratory class. AuPS Proceedings. 48:30P. Quiroga M, Price N (2016). Simulated in vivo Electrophysiology Experiments Provide Previ- ously Inaccessible Insights into Visual Physiology. J Undergrad Neurosci Educ. 15(1):A11-A17. Where applicable, the authors confirm that the experiments described here conform with the ethical requirements. PL02 Hunger Games – The Control of Appetite L. Heisler The Rowett Institute, University of Aberdeen, Aberdeen, UK Obesity has become one of the major health concerns of this century because of its prevalence and resistance to treatment. Specifically, one in four people in the UK are currently clinically obese. Significant progress has been made over the past decade in clarifying brain neurochemicals and regions regulating energy homeo- stasis. Among these is the key precursor polypeptide pro-opiomelanocortin (Pomc) within the homeostatic brain region the arcuate nucleus of the hypothalamus (ARC). The 5-hydroxytryptamine (5-HT, serotonin) 2C receptor (Htr2c; 5-HT2CR) agonist lorcaserin (Eisai Inc) is a new medication for obesity treatment that was recently launched in the USA. However, mechanism through which lorcaserin’s 2P Prize Lectures therapeutic effects are achieved remain to be elucidated. Here we clarify that the target of lorcaserin is 5-HT2CRs influencing the activity of ARC Pomc. Specifically, here we demonstrate that preventing Pomc production in the ARC (PomcNEO) is sufficient to abolish lorcaserin’s anorectic effects and that restoration of Pomc Htr2c specifically within a subset of ARC neurons expressing 5-HT2CRs (Pomc ) is sufficient to restore lorcaserin’s therapeutic effect. These findings illustrate that lorcaserin achieves it therapeutic benefit via activation of ARC Pomc peptides. To further clarify the brain circuit mediating lorcaserin’s appetite suppression, we next considered the receptors binding Pomc peptides. The melanocortin receptor most closely linked to appetite and body weight control is melanocortin4 receptor (Mc4r). Using a combination of viral and genetic technology, we reveal that lorca- serin suppresses appetite via action at PomcHtr2c signaling to Mc4rs. These findings reveal the mechanism underpinning the therapeutic benefit of the new obesity medication lorcaserin, via activation of a discrete melanocortin brain circuit. Work was supported by the Wellcome Trust, BBSRC and MRC Where applicable, the authors confirm that the experiments described here conform with the ethical requirements. PL03 Allosteric modulation of glutamate receptors S.F. Traynelis1,2, R. Perszyk1, S.A. Swanger3, C. Shelley4, A. Khatri1, G. Fernandez-Cuervo1,5, M.P. Epplin5, E. Garnier-Amblard5, H. Yuan1,2, D.S. Menaldino5, D.C. Liotta5 and L.S. Liebeskind5 1Pharmacology and Chemical Biology, Emory University School of Medicine, Atlanta, GA, USA, 2Center for Functional Evaluation of Rare Variants, Atlanta, GA, USA, 3Department of Biomedical Sciences and Pathobology, Virginia Tech Carilon Research Institute, Roanoke, VA, USA, 4Department of Biology, University of the South, Sewanee, TN, USA and 5Chemistry, Emory University, Atlanta, GA, USA NMDA receptors mediate a slow, Ca2+-permeable component of excitatory synaptic transmission in the central nervous system (CNS). These receptors are ligand- gated ion channels that are tetrameric assemblies of two glycine-binding GluN1 subunits and two glutamate-binding GluN2 subunits. There are four different genes encoding GluN2 (GRIN2A, GRIN2B, GRIN2C, GRIN2D), which are each expressed with a unique spatial profile throughout the CNS at different developmental stages. The different GluN2 subunits control the temporal signaling properties of the receptors, which likely allows different subunits to mediate different roles in development and circuit function. NMDA receptors require the binding of both glutamate and glycine in order to open the pore, which is triggered by protein rearrangements secondary to agonist-induced closure of a bi-lobed agonist binding domain that resembles a clamshell. We hypothesize that three key gating elements control opening of the ion-conducting pore following agonist binding. These elements include the 9 3P Prize Lectures highly conserved residues (SYTANLAAF) that comprise the extracellular end of the M3 transmembrane helix, the short two turn helix that is parallel to the plane of the membrane and precedes the M1 transmembrane helix, and the short linker preceding the M4 transmembrane helix (Amin et al., 2018; Chen et al., 2017; Gibb et al., 2018, Yuan et al., 2014). A considerable amount of data implicates these regions in gating, including the observation that regions of the genes encoding these portions of the polypeptide chain are devoid of variation in the human popu- lation, yet are a locus for disease-causing mutations in patients with neurological disease (XiangWei