In a groundbreaking collaborative study, Yu Jie's research group from the Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, and Ge Jingpeng's team from ShanghaiTech University have, for the first time, successfully isolated endogenous N-methyl-D-aspartate (NMDA) receptors from the entire brain tissue of mice. Moreover, they have conducted a comprehensive analysis of ten distinct assembly configurations of these receptors, shedding light on the structural diversity of endogenous receptors and identifying a previously unknown fully open state. The related research findings have been published in the esteemed journal Nature. NMDA receptors are pivotal in neurotransmission and the regulation of synaptic plasticity, and their malfunction can result in a spectrum of neurological disorders. Prior research has primarily depended on receptors generated through in vitro recombination, which poses challenges in accurately replicating the lipid environment within the body. This study revealed that receptors incorporating the GluN2A subunit are predominant throughout the brain, and their amino-terminal domains display considerable structural flexibility. Additionally, the research has, for the first time, captured a novel fully open conformation in endogenous GluN1-GluN2B receptors, offering vital structural insights into the mechanism by which ligand binding induces channel opening.