In the CNS, excitatory synaptic transmission is mediated by glutamate-activated ionotropic receptors, the largest subfamily of which are the N-methyl-D-aspartate receptors (NMDARs) encoded by seven GRIN genes. NMDARs are fundamental for the acquisition of various forms of synaptic plasticity, a key cellular mechanism of learning and memory, and they play an important role in CNS development. A significantly increased number of rare or de novo variants in GRIN genes have been found in patients with epilepsy, neurodevelopmental disorders, and neuropsychiatric diseases. The treatment of GRIN disorders is challenging because the number of different variants and the diversity of symptoms make it difficult to develop a universal treatment; instead, personalized therapy tailored to the individual patient variant is needed. Therefore, advanced molecular, functional, and pharmacological studies of GRIN variants and the use of corresponding animal models are current approaches to understanding the emergence and development of GRIN disorders in detail.

IPHYS contact person: Ladislav Vyklický, ladislav.vyklicky@fgu.cas.cz