A three-dimensional computer model exposes the brain’s neuropil, the hub where learning and memory begin.

Thought and memory take shape where the axon from one neuron contacts the dendrite of another at a junction called the synapse, as depicted here.

When Johann Strauss II composed The Blue Danube in the 1860s, he could hardly have imagined that scientists in the future would watch, captivated, as a computer-generated brain waltzed to his tune.

Neuroscientist Terry Sejnowski wowed the crowd doing just that during a lecture last year at the Salk Institute for Biological Studies, in La Jolla, California. Sejnowski, an HHMI investigator at the Salk, presented his lab’s model: a segment of a brain floating dreamily around the screen as different parts of its cellular machinery—channels, connectors, and organelles—emerged around a single starting filament.

Sejnowski will use the model not only to entertain, but also—sans musical accompaniment—to study how the brain learns and remembers.

“This is the beginning of a whole new era,” he says. “For the first time, it gives us a three-dimensional, complete reconstruction in which we can, literally, include the impact of every single important molecule.”

Learning and memory depend on nerve cells and support cells called astrocytes. Nerves have “output” channels—long slender axons that reach out to other nerves—and “input” channels—branching dendrites that collect incoming signals. Thought and memory take shape where the axon from one nerve contacts the dendrite of another at a junction called the synapse.

Waltz through a computer model of the brain’s neuropil.

At the synapse, the first nerve’s axon sends out a signal in the form of molecules called neurotransmitters. These chemicals cross the junction and are picked up by the second nerve’s dendrites. Astrocytes then mop up excess neurotransmitter.

The brain’s estimated one quadrillion synapses are the most numerous and complex structures involved in learning and memory, Sejnowski says. How the frequency and strength of transmissions are controlled and communicated remains a mystery. “If you don’t understand that, you’re never going to understand how the brain works.”

Axons and dendrites meet in a region called the neuropil. The walls of the Computational Neurobiology Laboratory, which Sejnowski heads, are adorned with huge black-and-white electron micrographs of cross sections of the neuropil—a dense conglomerate of bubble-like vesicles, wrinkled mitochondrial membranes, and other cellular components. “It’s all jumbled … it’s very hard to understand,” Sejnowski says.

Sejnowski and postdoctoral fellow Justin Kinney are investigating how synapses influence one another. They wondered if neurotransmitters from one synapse could spill over and activate neighboring dendrites as well. The answer, they reasoned, would depend on whether each synapse is surrounded by astrocytes, which would absorb leftover neurotransmitter. Those without astrocytes would leave neurotransmitters to diffuse into nearby synapses.

Image: Kristen Harris (UT at Austin), Mary Kennedy (Caltech), and the Sejnowski Lab (Salk Institute)

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