The temporal pattern of synaptic activation determines the longevity of structural plasticity at dendritic spines

Learning is thought to involve physiological and structural changes at individual synapses. Synaptic plasticity has predominantly been studied using regular stimulation patterns, but neuronal activity in the brain normally follows a Poisson distribution. We used two-photon imaging and glutamate uncaging to investigate the structural plasticity of single dendritic spines using naturalistic activation patterns sampled from a Poisson distribution. We showed that naturalistic activation patterns elicit structural plasticity that is both NMDAR and protein synthesis-dependent. Furthermore, we uncovered that the longevity of structural plasticity is dependent on the temporal structure of the naturalistic pattern. Finally, we found that during the delivery of the naturalistic activity, spines underwent rapid structural growth that predicted the longevity of plasticity. This was not observed with regularly spaced activity. These data reveal that different temporal organizations of the same number of synaptic stimulations can produce rather distinct short and long-lasting structural plasticity.