The Temporal Pattern of Synaptic Activation Determines the Longevity of Structural Plasticity at Single Dendritic Spines

Abstract

Individual synapses are the points at which information is passed between neurons, yet it is unknown how the diverse patterns of activity that are observed in vivo effect plasticity at the level of single inputs. Here, we aimed to determine what are the structural plasticity consequences of naturalistic patterns of activity at single spines, as these reflect changes in synaptic efficacy. Utilizing two- photon fluorescence imaging and glutamate uncaging, we studied structural plasticity of individual CA1 hippocampal dendritic spines using activation patterns sampled from a Poisson distribution, which resemble endogenous firing patterns from their CA3 inputs. We found that while the majority of inputs initially undergo structural changes, the robustness of this plasticity is determined by the timing structure of the Poisson sampled naturalistic stimulation patterns. Further, we found that structural plasticity elicited by these naturalistic patterns is both NMDAR and protein synthesis dependent, consistent with requirements for other forms of plasticity. Lastly, we found that during the delivery of naturalistic activity patterns, spines underwent rapid and dynamic structural growth that predicted the longevity of plasticity, which was not the case during non-naturalistic stimulation protocols. These data suggest that dendritic spines are able to integrate incoming temporal information and accordingly modulate the longevity of plasticity that is induced. HighlightsO_LINaturalistic stimulation of single dendritic spines of CA1 hippocampal neurons induces long lasting structural plasticity that depends on the temporal distribution of the synaptic events. C_LIO_LIStructural plasticity induced by naturalistic stimulation patterns requires NMDA receptor activation and new protein-synthesis. C_LIO_LIRapid spine structural dynamics during naturalistic activity, but not regular patterns, predict the longevity of subsequent structural plasticity. C_LI