Spotlight: Sheng

What is the architecture of memory?

In the brain, as in certain elegant kinds of architecture, form follows function; understanding how a synapse is put together will tell you what it does and how it works.

A synapse—that minute connection between two brain cells—is thought to comprise several hundred or perhaps even a thousand distinct proteins. The goal of Morgan Sheng's lab is to identify and understand all of them. What is the protein's structure? Where does it fit in the synapse—what does it bind to or support? How is it regulated? What happens if you have more of it, or get rid of it altogether? Who does it talk to? And is it involved in any diseases? As Professor Sheng observes, "The genome is full of bureaucrats"—genetic players who perform some limited work but whose absence would hardly be noticed. The aim is to understand which proteins are critical to the serious work of learning and memory.

Already, the Sheng lab has discovered a specific set of proteins that are physically linked to each other to form the essential architecture of the synapse. Moreover, they discovered that these molecular building blocks move in and out of synapses with amazing dynamism, strengthening and weakening the synaptic connections as they go. Since this synaptic strengthening and weakening is the essential mechanism for storing memories in the brain, Professor Sheng's discovery is crucial step toward understanding how memories are made.

The lab's progress in decoding the synaptic architecture may also lead to a deeper understanding of how synaptic connections go wrong. For example, the degeneration of synapses is a hallmark of Alzheimer's disease. Schizophrenia may involve a subtler disordering in synaptic development and functioning. In both cases, defects in the proteins that make up the synapses may turn out to be the culprits. And just as crippling diseases like muscular dystrophy are linked to defects in the proteins comprising muscle-cell synapses, a host of psychiatric conditions, from autism to psychosis, may hinge on mutations of synaptic proteins in the brain.