The mammalian brain not only undergoes rapid synaptic changes critical for information encoding, but also is capable of maintaining most synaptic connections important for long-term information storage. Dendritic spines are the postsynaptic sites of most excitatory synapses in the mammalian brain. In this talk, I will discuss how novel experiences regulate the remodeling of dendritic spines, as well as the role of sleep in dendritic spine plasticity and maintenance. I will also discuss how inhibitory neurons and glial cells regulate the balance between synaptic plasticity and stability in the cortex. Because synapses are the key elements for information acquisition and retention, understanding how they are formed and maintained in the living brain provides important insights into the structural basis of learning and memory.