NMDA receptors and PSD-95 are found in attachment plaques in cerebellar granular layer glomeruli.

Abstract

N-methyl-D-aspartate (NMDA) receptors mediate long-term changes in excitatory synapses in response to glutamate release. In the cerebellar granular layer, most glutamatergic synapses are formed between mossy terminals and granule cell dendrites, which together with some other components, make up complex glomerular structures. Glomeruli contain numerous attachment plaques (or puncta adherentia), which are sites of adhesion between cells. These structures are found mainly between granule cell dendrites, and probably help maintain the integrity of glomeruli. Attachment plaques contain adhesive proteins such as cadherins. In this study, we show that NMDA receptors are common at these attachment plaques, in addition to being found at synapses. We used four different antibodies to the NMDA receptor subunit, NR1, and another to NR2A/B. In contrast, labelling for an alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) glutamate receptor antibody was seen only in a few attachment plaques, although AMPA receptors were seen frequently at glomerular synapses. We also show that substantial levels of the NMDA receptor-associated protein, PSD-95, are found in both synapses and attachment plaques. One way that NMDA receptors mediate changes in synapses is through effects on synaptic cadherins, which change their adhesive properties in response to NMDA receptor activation and consequently may alter synaptic function. The presence of NMDA receptors in attachment plaques suggests that these receptors mediate changes in the adhesive properties of these plaques, similar to this function in synapses.