Annotation: NMDA receptors, whose subunits are encoded by GRIN genes, are ionotropic glutamate receptors critical for synaptic plasticity. Variants in GRIN genes have been identified in patients with complex neurodevelopmental disorders, but the disease mechanisms involved are poorly understood, and treatment options remain limited. There has been progress in describing how different pathogenic GRIN gene variants alter NMDA receptor function. The current challenge is to learn how such changes influence synaptic transmission and circuit function, and how to restore appropriate NMDA receptor signalling in patients. Using in-vitro patch-clamp electrophysiology in heterologous expression systems, and multi-level study of mouse models carrying clinically relevant GRIN2B variants, we find that synaptic phenotypes of patient GRIN gene variants involve altered NMDA receptor subunit composition, with implications for the overall circuit-level outcome and for the design of pharmacological or genetic treatments. The study of GRIN gene-related disorders reveals fundamental principles of synapse function and brain development.

Biography: Dr. Smejkalova conducted her PhD research in the laboratory of Dr. Catherine Woolley at Northwestern University, USA. She completed her postdoctoral training in the Laboratory of Cellular Neurophysiology, IPHYS, under Prof. Ladislav Vyklický, and as a visiting postdoctoral scientist in the laboratory of Dr. Steven Mennerick at Washington State University in St. Louis, USA. Dr. Smejkalova is currently a researcher in the Laboratory of Cellular Neurophysiology, IPHYS, and her research focuses on the role of synaptic dysfunction in the etiology of neurodevelopmental disorders and on the modulation of synaptic transmission by endogenous neurosteroids.