AbstractOne of the biggest remaining mysteries of science is inside our heads: how does nature wire up a high-performance computer with­out having a detailed blueprint specifying the location and strength of every connection? It is assumed that local connectivity in our cor­tex is at first random, and during develop­ment undergoes refinement until only the 'right' connections are left over. But how can the brain tell 'right' from 'wrong' connections? The majority of excitatory connections are

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... rmed on dendritic spines, tiny excrescenc­es that cover almost the entire dendritic sur­face of most neurons. Since their discovery by Ramón y Cajal in 1896, neuroscientists have been fascinated by these structures, which ultimately determine which neurons in the brain become connected and form function­al networks. Here we review the many im­portant functions of spines and explain why electrical and biochemical processes in these tiny structures are thought to be crucial for the plasticity of the brain.