Dendritic spine dynamics regulate the long-term stability of synaptic plasticity.

Long-term synaptic plasticity requires postsynaptic influx of Ca²⁺ and is accompanied by changes in dendritic spine size. Unless Ca²⁺ influx mechanisms and spine volume scale proportionally, changes in spine size will modify spine Ca²⁺ concentrations during subsequent synaptic activation. We show that the relationship between Ca²⁺ influx and spine volume is a fundamental determinant of synaptic stability. If Ca²⁺ influx is undercompensated for increases in spine size, then strong synapses are stabilized and synaptic strength distributions have a single peak. In contrast, overcompensation of Ca²⁺ influx leads to binary, persistent synaptic strengths with double-peaked distributions. Biophysical simulations predict that CA1 pyramidal neuron spines are undercompensating. This unifies experimental findings that weak synapses are more plastic than strong synapses, that synaptic strengths are unimodally distributed, and that potentiation saturates for a given stimulus strength. We conclude that structural plasticity provides a simple, local, and general mechanism that allows dendritic spines to foster both rapid memory formation and persistent memory storage.