Theta Stimulation Polymerizes Actin in Dendritic Spines of Hippocampus

Abstract

It has been proposed that the endurance of long-term potentiation (LTP) depends on structural changes entailing reorganization of the spine actin cytoskeleton. The present study used a new technique involving intracellular and extracellular application of rhodaminephalloidin to conventional hippocampal slices to test whether induction of LTP by naturalistic patterns of afferent activity selectively increases actin polymerization in juvenile to young adult spines. Rhodamine-phalloidin, which selectively binds to polymerized actin, was detected in perikarya and proximal dendrites of CA1 pyramidal cells that received low-frequency afferent activity but was essentially absent in spines and fine dendritic processes. Theta pattern stimulation induced LTP and caused a large (threefold), reliable increase in labeled spines and spine-like puncta in the proximal dendritic zone containing potentiated synapses. The spines frequently occurred in the absence of labeling to other structures but were also found in association with fluorescent dendritic processes. These effects were replicated (Ͼ10-fold increase in labeled spines) using extracellular applications of rhodamine-phalloidin. Increases in labeling appeared within 2 min, were completely blocked by treatments that prevent LTP induction, and occurred in slices prepared from young adult rats. These results indicate that near-threshold conditions for inducing stable potentiation cause the rapid polymerization of actin in mature spines and suggest that the effect is both sufficiently discrete to satisfy the synapse-specificity rule of LTP as well as rapid enough to participate in the initial stages of LTP consolidation.

Extracellular proteolysis by matrix metalloproteinase-9 drives dendritic spine enlargement and long-term potentiation coordinately

“…After TBP, there is an immediate increase in both spine size and EPSPs. The former is presumably attributable to rapid actin remodeling, at least partially mediated by cofilin inactivation, occurring seconds to minutes after LTP induction (4,5,20,24,(32)(33)(34), and the latter likely to rapid phosphorylation of AMPA receptors (AMPARs) (35). The MMP blockers had no effect on the immediate, TBP-triggered changes in spine size and potentiation, indicating that such rapid plasticity is mechanistically independent of MMP proteolysis.…”

Synaptic Strength of Individual Spines Correlates with Bound Ca2+–Calmodulin-Dependent Kinase II

“…Accordingly, actin depolymerizing agents dramatically reduce the amount of CaMKII␣ found at spines (Allison et al, 2000;Asrican et al, 2006). Importantly, the amount of F-actin in spines increases after LTP induction (Okamoto et al, 2004;Lin et al, 2005) providing more targets for CaMKII binding. This binding is likely to contribute to the increase in the BA of CaMKII after LTP and for the correlation of the BA with spine size reported in this study.…”

“…An enhanced density of the kinase at the PSD (Otmakhov et al, 2004) and kinase self-association (Hudmon et al, 2005) may account for the excessive amount of bound CaMKII responsible for the increased BF. Slowly this excessive amount may leave the spine, bringing the BF back to the initial prepotentiated level while the BA of CaMKII remains elevated proportionally with the increased PSD (Ostroff et al, 2002) and F-actin mesh (Lin et al, 2005).…”

Synaptic plasticity in early aging

“…We prefer the original Lynch and Baudry proposal that changes in receptor number are secondary to changes in the size of the synaptic zone (the post synaptic density, psd), which themselves are secondary to alterations in spine morphology. The original impetus for this idea came from ultrastructural studies showing that shifts in spine and psd morphology accompany LTP (Lee et al, 1980), an observation subsequently greatly expanded by analyses with electron microscopic (Yuste and Bonhoeffer, 2001 for review) and newly developed light microscopic Lin et al, 2005) methods.…”