LTP Promotes a Selective Long-Term Stabilization and Clustering of Dendritic Spines

Abstract

Dendritic spines are the main postsynaptic site of excitatory contacts between neurons in the central nervous system. On cortical neurons, spines undergo a continuous turnover regulated by development and sensory activity. However, the functional implications of this synaptic remodeling for network properties remain currently unknown. Using repetitive confocal imaging on hippocampal organotypic cultures, we find that learning-related patterns of activity that induce long-term potentiation act as a selection mechanism for the stabilization and localization of spines. Through a lasting N-methyl-D-aspartate receptor and protein synthesis–dependent increase in protrusion growth and turnover, induction of plasticity promotes a pruning and replacement of nonactivated spines by new ones together with a selective stabilization of activated synapses. Furthermore, most newly formed spines preferentially grow in close proximity to activated synapses and become functional within 24 h, leading to a clustering of functional synapses. Our results indicate that synaptic remodeling associated with induction of long-term potentiation favors the selection of inputs showing spatiotemporal interactions on a given neuron.

Activity-Dependent Structural Plasticity of Perisynaptic Astrocytic Domains Promotes Excitatory Synapse Stability

“…We first confirmed that the application of LTP-inducing Ɵ burst stimulation induced spine head enlargements (of more than 20% growth in size). Indeed, 30 min poststimulus, we found 40% of the spines to be enlarged [31] ( Figure 3B). This effect was blocked by the NMDAR blocker D-AP5 ( Figure 3B), indicating that Ɵ burst stimulation produced genuine postsynaptic, NMDAR-dependent LTP.…”

“…Structural mechanisms are less understood, and their causal link to functional mechanisms is still unclear. Current concepts of synapse structural plasticity propose that following LTP induction paradigms, postsynaptic spines increase their turnover and that the subset of spines that have been functionally potentiated become very stable structures that persist over days [31,44,45]. The mechanisms promoting spine stability remain largely unknown and could involve astrocytic perisynaptic processes, as they are known to increase their synaptic coverage after LTP [24] and are functionally implicated in LTP mechanisms [14,18].…”

“…To assess the effect of synaptic activity on PAP movements, we first monitored PAP motility in the presence of either the cholinergic agonist carbachol, which induces theta activity [31], or the sodium channel blocker tetrodotoxin (TTX), which represses neuronal activity. The addition of carbachol significantly increased the MI, whereas TTX lowered the MI (Figure 2A), suggesting that neuronal activity was necessary and sufficient for PAP motility.…”

“…To test this, we applied a short theta-burst stimulation (Ɵ burst ) protocol (five trains at 5 Hz of four 100 Hz pulses, repeated twice with a 10 s interval) that has been shown to induce LTP in hippocampal slice cultures [31] (Figure 3A). Similarly to low-frequency stimulation, Ɵ burst stimulation significantly increased PAP motility ( Figure 3A).…”

“…Synaptic LTP is known to lead to an increase in size of activated spines [31,36]. This provided us with a tool to check whether synaptic potentiation-induced increased PAP motility is synapse specific.…”