A simple and elegant way to enable the process of learning

As it develops and stores information, the brain undergoes physical changes in microcircuitry. These three-dimensional profiles show intensity of recycling endosome cargo in a single dendritic spine, with a scale from low (purple) to high (red), as well as long term potentiation (LTP) of synaptic strength over time (left to right).

Unlike your computer's memory chips, whose circuits are etched into a solid slab of silicon, real brain circuits change shape as they learn. HHMI investigator Michael D. Ehlers and his colleagues at Duke University are themselves learning how neurons remold their connections, and they may have identified the brain's favored sculpting tool.

Ehlers' team focuses on dendrites—the neuronal branches that support the nerve cell's connections to other neurons—and in particular on the tiny spines that sprout on dendrites and act as the receiving stations for incoming signals. These dendritic spines, Ehlers explains, are the centers of neuronal rewiring—i.e., learning.

The spines contain receptors for neurotransmitters, notably the AMPA receptor proteins that accumulate in the surrounding membranes. Several years ago, Ehlers' group discovered that that these receptors migrate to the membrane by way of tiny vesicles called recycling endosomes. "The way you functionally enhance the synapse (the connection between neighboring neurons) is to get more AMPA receptors there," says Ehlers.

In a paper published in the December 7, 2006, issue of Neuron, Ehlers and colleagues extended those earlier findings. Using advanced light- and electron-microscopy techniques, they found that recycling endosomes provide not only the AMPA receptors but also the membrane components that neurons need to shape their connections. This discovery, he says, emerged from no small amount of free thinking. "No one had ever asked ‘Where does the membrane come from?'"

The findings are already simplifying the way neuroscientists think about learning and brain circuitry, says Ehlers. "You don't need a hundred different mechanisms to mobilize a hundred different molecules. Maybe you just need one core transport mechanism that delivers a prepackaged set of molecules and membranes to the synapse." He hopes the discovery may lead to new avenues for restoring or augmenting the brain's plasticity—its ability to mobilize healthy nerve cells to compensate for damage caused by disease or injury.

Scientific Image: Mikyoung Park and Michael Ehlers