Homosynaptic plasticity induction causes heterosynaptic changes at the unstimulated neighbors in an induction pattern and location-specific manner.

Dendritic spines are highly dynamic structures whose structural and functional fluctuations depend on multiple factors. Changes in synaptic strength are not limited to synapses directly involved in specific activity patterns. Unstimulated clusters of neighboring spines in and around the site of stimulation can also undergo alterations in strength. Usually, when plasticity is induced at single dendritic spines with glutamate uncaging, neighboring spines do not show any significant structural fluctuations. Here, using two-photon imaging and glutamate uncaging at single dendritic spines of hippocampal pyramidal neurons, we show that structural modifications at unstimulated neighboring spines occur and are a function of the temporal pattern of the plasticity-inducing stimulus. Further, the relative location of the unstimulated neighbors within the local dendritic segment correlates with the extent of heterosynaptic plasticity that is observed. These findings indicate that naturalistic patterns of activity at single spines can shape plasticity at nearby clusters of synapses, and may play a role in priming local inputs for further modifications.