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. In the central nervous system, excitatory contacts between neurons occur mainly on postsynaptic protrusions called dendritic spines. For decades, these structures have been considered static, and the adaptive properties of neuronal networks were thought to be only due to changes in the strength of neuronal connections. But recently, new imaging techniques used on living neurons revealed that spines and synapses are dynamic structures that undergo continuous turnover and can be formed or eliminated as a function of activity. The functional consequences of this structural remodeling, however, were still unknown. This work shows that application of learning related paradigms (such as induction of long-term potentiation or rhythmic activity) to hippocampal neurons allows them to operate a selection of synaptic inputs that show coincident activity. This is done through a competitive mechanism that promotes a selective stabilization of synapses activated by the learning paradigm and a replacement of non-activated inputs by new spines. Furthermore these new dendritic spines preferentially grow in close proximity to activated synapses and become functional. These findings provide evidence that learning related paradigms play a major role in shaping the structural organization of synaptic networks by promoting their specificity.