Long-term potentiation (LTP) has long been considered as an important cellular mechanism for learning and memory. LTP expression involves NMDA receptor-dependent synaptic insertion of AMPA receptors (AMPARs). However, how AMPARs are recruited and anchored at the postsynaptic membrane during LTP remains largely unknown. In this study, using CRISPR/Cas9 to delete the endogenous AMPARs and replace them with the mutant forms in single neurons, we have found that the amino-terminal domain (ATD) of GluA1 is required for LTP maintenance. Moreover, we show that GluA1 ATD directly interacts with the cell adhesion molecule neuroplastin-65 (Np65). Neurons lacking Np65 exhibit severely impaired LTP maintenance, and Np65 deletion prevents GluA1 from rescuing LTP in AMPARs-deleted neurons. Thus, our study reveals an essential role for GluA1/Np65 binding in anchoring AMPARs at the postsynaptic membrane during LTP.

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Hematological and biochemical blood traits have been linked to brain structural characteristics in humans. However, the relationship between these two domains has not been systematically explored in nonhuman primates, which are crucial animal models for understanding the mechanisms of brain function and developing therapeutics for various disorders. Here we investigated the associations between hematological/biochemical parameters and the brain’s gray matter volume and white matter integrity derived from T1-weighted and diffusion magnetic resonance imaging in 36 healthy macaques. We found that intersubject variations in basophil count and hemoglobin levels correlated with gray matter volumes in the anterior cingulum, prefrontal cortex, and putamen. Through interactions between these key elements, the blood parameters’ covariation network was linked with that of the brain structures, forming overarching networks connecting blood traits with structural brain features. These networks exhibited hierarchical small-world architecture, indicating highly effective interactions between their constituent elements. In addition, different subnetworks of the brain areas or fiber tracts tended to correlate with unique groups of blood indices, revealing previously unknown brain structural organization. These results provide a quantitative characterization of the interactions between blood parameters and brain structures in macaques and may increase the understanding of the body–brain relationship and the pathogenesis of relevant disorders.

Although xenotransplantation has revolutionarily developed based on the usage of genome-edited pigs, it is still unknown whether these pigs and their offspring remains genomic stable. Here, we show that GGTA1-knockout (GTKO) pigs accumulated an average of 1205 genome-wide genetic mutations, and their filial 1 offspring contained an average of 18 de novo mutations compared with wild control and their parents, respectively. The majority of mutations were annotated in intergenic regions without altering protein functions and predicted off-target mutations. RNA-sequencing analysis and phenotype observation indicated that accumulated mutations may have a limited influence on GTKO pigs and most genetic mutations in GTKO pigs can be explained by electrotransfection of plasmids into cells. This is the first report that the genetic mutations of genome-edited pigs are inherited stably by their filial generation and provide a reference for safe application and the standard approach to breeding genome-edited pigs for xenotransplantation.