In vivo, competitive blockade of N-methyl-D-aspartate receptors induces rapid changes in filamentous actin and drebrin A distributions within dendritic spines of adult rat cortex

In vitro studies have demonstrated that prolonged N-methyl-d-aspartate receptor (NMDAR) blockade triggers a homeostatic up-regulation of NMDARs at synapses. Such upregulation can also be seen within 30 min in vivo in adult rats, implicating trafficking of reserve pools of NMDARs. Here, we evaluated the involvement of filamentous actin (F-actin), the major cytoskeletal component in spines, in this rapid in vivo homeostatic response, using biotinylated phalloidin as its probe. We also immuno-labeled spines for drebrin A, an F-actin-binding protein found at excitatory synapses and with a proposed role of modulating F-actin’s cross-linking with one another and interactions with NMDARs. Quantitative 2-D analysis of ultrastructural images revealed that NMDAR blockade increased filamentous actin labeling per spine by 62.5% (P