For example, we have previously reported that there is a smaller Atractylenolide-III population of GluA2 a ached to N-linked high mannose containing glycans in dorsolateral prefrontal cortex in patients with schizophrenia, which we interpreted as consistent with accelerated forward trafficking of the GluA2-containing AMPA receptors. Glycosylation may also affect neurodevelopment: GluA2 in mouse hippocampus expresses the human natural killer-1 glycol-epitope, which may be essential for dendritic spine morphogenesis in developing neurons. Studies aimed at understanding the function of mammalian brain have predominantly used rodent models. However, given the Benzoylpaeoniflorin significant evolutionary distance between rodents and humans, it remains unclear to what extent data from rodent studies can be used to understand human disorders associated with abnormalities of glutamate neurotransmission. In the current study, we asked if one can use findings from animal models to uncover roles that glycans/glycoproteins may play in normal brain and begin to address dysfunction of glycosylation in pathological conditions, given the rapid rate of human brain evolution and the estimated rate of change in the brain- specific glycoproteome. To that end, we compared N-glycosylation in brain of GluA1-4 between four mammalian species, with the hypothesis that we would observe evolutionarily distinct pa erns of glycosylation of AMPA receptors, which in turn might reflect intrinsic differences in biosynthesis, processing, trafficking, or interaction of the receptor subunits with cellular and extracellular partners. In this study, we characterized the glycosylation of AMPA receptor subunits in the frontal cortex from four mammalian species using Western blot analysis, following enzymatic deglycosylation and by lectin binding assays. As we have previously shown in the human, we found that two AMPA receptor subunits, GluA2 and GluA4, are sensitive to deglycosylation with Endo H and PNGase F, consistent with large molecular masses of glycans a ached to these subunits. When we enriched for glycosylated proteins using lectin binding assay, we were able to detect glycans a ached to all four AMPA receptor subunits. We also noted species-specific pa erns of glycosylation, although these were generally modest differences. N-linked glycosylation occurs in the ER with subsequent modification in the Golgi apparatus; movement of the AMPA subunits through the ER and Golgi can be inferred by their sensitivity to Endo H. Glycoproteins that contain high mannose and hybrid chains are sensitive to Endo H-driven deglycosylation while they are in the ER and in proximal regions of the Golgi complex. In the mid Golgi apparatus, glycans are modified to more complex structures which become Endo H insensitive. However, all N-linked glycans are sensitive to PNGase F, and only the addition of a1,3fucose in invertebrates and plants has been described to confer resistance to this glycosidase. This study is consistent with our previous findings that in the human frontal cortex, GluA2 and GluA4 are the only subunits sensitive to deglycosylation by Endo H and PNGase F. Analysis of deglycosylation pa erns revealed that a larger population of GluA2 in human and macaque contained Endo H-sensitive high mannose or hybrid glycans.