Drebrin a content correlates with spine head size in the adult mouse cerebral cortex

Abstract

Synaptic activities alter synaptic strengths at the axospinous junctions, and such changes are often accompanied by changes in the size of the postsynaptic spines. We have been exploring the idea that drebrin A, a neuron-specific actin-binding protein localized on the postsynaptic side of excitatory synapses, may be a molecule that links synaptic activity to the shape and content of spines. Here, we performed electron microscopic immunocytochemistry with the nondiffusible gold label to explore the relationship among levels of drebrin A, the NR2A subunit of N-methyl-D-aspartate receptors, and the size of spines in the perirhinal cortex of adult mouse brains. In contrast to the membranous localization within neonatal spines, most immunogold particles for drebrin A were localized to the cytoplasmic core region of spines in mature spines. This distribution suggests that drebrin within adult spines may reorganize the F-actin network at the spine core, in addition to its known neonatal role in spine formation. Drebrin A-immunopositive (DIP) spines exhibited larger spine head areas and longer postsynaptic densities (PSDs) than drebrin A-immunonegative (DIN) spines (P < 0.001). Furthermore, spine head area and PSD lengths correlated positively with drebrin A levels (r = 0.47 and 0.40). The number of synaptic NR2A immunolabels was also higher in DIP spines than in DIN spines, whereas their densities per unit lengths of PSD were not significantly different. These differences between the DIP and the DIN spines indicate that spine sizes and synaptic protein composition of mature brains are regulated, at least in part, by drebrin A levels.

Activity of the AMPA receptor regulates drebrin stabilization in dendritic spine morphogenesis

“…The study using glutamate uncaging has shown that functional AMPARs are sparsely distributed in dendritic filopodia and thin spines but abundant in mushroom-shaped large spines, indicating the correlation between spine volume and its expression of functional AMPAR (Kasai et al, 2003;Matsuzaki et al, 2001). Given that drebrin content is correlated with spine volume (Kobayashi et al, 2007), our present study suggests that the rapid turnover of filopodia is due to an insufficient amount of stable drebrin, whereas spine persistence is due to an AMPAR-regulated abundance of stable drebrin. This is consistent with evidence that shows that AMPAR activity contributes to spine maintenance (McKinney et al, 1999).…”

Plasticity of Dendritic Spines: Subcompartmentalization of Signaling

“…Recent work suggests that drebrin may alter the properties of actin filaments, rendering them resistant to depolymerization (85). Moreover, larger spines with increased PSD size are enriched in drebrin A (86), suggesting that it may play a role in stabilizing spine enlargement induced by LTP (87). …”

Synaptic protein expression in the medial temporal lobe and frontal cortex following chronic bilateral vestibular loss

“…Synaptophysin is a synaptic vesicle glycoprotein that is involved in the release of neurotransmitter vesicles (Fuentes-Santamaria et al, 2007); SNAP-25 (''synaptosome-associated protein of 25 kDa'') is a presynaptic nerve terminal protein involved in vesicle exocytosis (Delgardo-Martinez et al, 2007); drebrin (''developmentally regulated brain protein'') is a neuronal F-actin binding protein involved in axonal and dendritic plasticity (Kobayashi et al, 2007); and NF-L is a member of the neurofilament protein family, which is often used as a biomarker for cell death and axonal loss (Petzold et al, 2007;Barry et al, 2007). These four proteins were chosen for investigation for two reasons: (1) as a precursor to a larger gene microarray analysis, to determine the likelihood that genes and proteins related to synaptic transmission may change in the medial temporal lobe following BVD, since none have been investigated in this context previously; and (2) because these four proteins have been implicated in synaptic plasticity processes, such as axonal terminal remodelling (SNAP-25;Osen-Sand et al, 1993), activity-dependent synapse formation (synaptophysin; Tarsa and Goda, 2002), dendritic spine morphogenesis (drebrin; Sekino et al, 2007) and axonal transportation (NF-L).…”