Nerve connections come ready to assemble

Catering to the do-it-yourself crowd, a few companies sell the lumber, doors, windows, and everything else needed to build a home. They’ll even deliver the home-building kit to a person’s future doorstep.

Similarly, nerve cells seem to package key components of synapses—the specialized structures that allow the cells to communicate with one another—and collectively ship the material to points where these complexes take shape. “Everything is bundled [and transported] together.

The final stage of construction probably happens at the site of cell-cell contact,” says Stephen J. Smith of Stanford University. This new view of synapse assembly has emerged from efforts to study the cellular connections as they form—a phenomenon challenging to observe. In their latest work, Smith and his Stanford colleagues Susanne E. Ahmari and JoAnn Buchanan were following a synaptic protein called VAMP. This molecule helps form vesicles, sacs containing the chemicals that one nerve cell releases to excite the next. The researchers fused the gene for VAMP to the gene for a fluorescent protein, creating a hybrid gene encoding a green-glowing VAMP.

A nerve cell makes VAMP in its main body and then, by attaching the protein to cellular railroad tracks called microtubules, sends it along axons, the thin extensions that nerve cells produce to reach out to other cells. Smith and his colleagues assumed that a nerve cell delivers individual VAMP molecules, or small clusters of them, to sites where an axon meets another nerve cell. There, VAMP would join other molecules and become part of a synapse.

While watching the fluorescent VAMP travel through axons, however, the scientists realized that the microtubules were transporting packets containing large amounts of the protein, many more molecules than needed to form a single synaptic vesicle. They then found that the mobile packets usually held other proteins required to build the signal-sending, or presynaptic, side of the synapse.

The researchers contend that nerve cells initially gather many, if not all, components of this part of the synapse into a single transportable package, instead of dispatching parts piece by piece. This strategy “might lend itself to the rapid construction of synapses, perhaps [aiding] learning and memory,” says Smith.

In the recent experiments, described in the May Nature Neuroscience, the Stanford team studied brain cells growing and forming synapses in laboratory dishes. The scientists now plan to look for signs of synaptic building kits in newborn rodents, whose brains are rapidly making new connections.

Morgan H. Sheng of Massachusetts General Hospital in Boston notes that investigators still need to determine if the kits contain all the required elements. “I don’t think we can safely say that the whole presynaptic [complex] is transported in a packet, but I do think there’s some kind of preassembled compartment,” he says.

Sheng points out that Smith’s group only studied the assembly of the pre-synaptic structure, which differs considerably from the signal-receiving apparatus of the synapse’s other side. “It’ll be quite interesting to know whether the postsynaptic [complex] is also constructed from pre-existing, partly assembled packets,” says Sheng.