Synapses form trillions of connections in the brain. Long-term potentiation (LTP) is a cellular mechanism vital for learning that modifies the strength and structure of synapses. Three-dimensional electron microscopy reveals distinct pre- to post-synaptic arrangements. Strong active zones have tightly docked presynaptic vesicles, weak active zones have loose or non-docked vesicles, and nascent zones have a postsynaptic density but no presynaptic vesicles. LTP can be temporarily saturated, which prevents further increases in synaptic strength. We have used 3D reconstruction from serial section electron microscopy to discover how the plasticity of nascent zones provides a time dependent and synapse-specific expansion of active zones during LTP. This expansion ultimately encourages the formation of highly effective dendritic spine clusters regulated by the spine apparatus. I will introduce our rat model system with knockout of synaptopodin as a basis for investigating the cluster hypothesis. We hypothesize that the saturation of LTP protects recently formed memories and that regrowth of nascent zones accounts for the advantage of spaced over massed learning.