GRIN1, encoding the obligatory GluN1 subunit of N-methyl-D-aspartate receptors (NMDARs), is crucial for synaptic transmission and plasticity, as well as neural circuit development [1]. NMDARs are a subtype of ionotropic glutamate receptors, and their function is integral to normal brain development and cognitive function [1].

In mice, disruption of Grin1 within corticotropin-releasing factor (CRF) neurons in the central amygdala enhanced fear memory, suggesting its role in fear-related behaviors [2]. Loss-of-function mutations in Grin1 in male Grin1-/-knockdown mice led to volume reductions in dopaminergic structures early in development, with delayed changes in limbic and white matter structures, and evidence of degenerating neurons in the mature brain, indicating ongoing cell loss due to NMDAR hypofunction [3]. Grin1 Y647S/+ mice, a model of GRIN1-related neurodevelopmental disorder, showed reduced whole-brain GluN1 levels, deficient NMDAR-mediated synaptic transmission in the hippocampus, and exhibited spontaneous seizures, altered vocalizations, muscle strength, sociability, and problem-solving [4].

In conclusion, Grin1 is essential for normal neural function, playing a key role in synaptic transmission, plasticity, and neural circuit development. Studies using gene-knockout (KO) mouse models have revealed its significance in various aspects of neural development, function, and disease, such as in fear-related behaviors, neurodegeneration, and neurodevelopmental disorders [2,3,4].