Measuring molecules at a single synapse gives clues to how memories become long term.

When neurons fire in the brain, they exchange signals through tiny buds known as spines. Signaling strength can fluctuate rapidly, but some changes lasting minutes or longer are thought to encode long-term memories. To better understand what’s happening in those extended moments, biophysicist Ryohei Yasuda images living spines as signaling occurs, as seen in this series of photos.

Postdoctoral researcher Hong Wang flits in and out of a dark, curtained-off area in Ryohei Yasuda’s lab at Duke University. Wang is fiddling with a slice of mouse brain that floats in an electrolyte broth similar to the fluid that naturally bathes the brain. Once she has the setup just right, she will use one of Yasuda’s specially built microscopes to look at enlargement of a single neuron’s spine, a tiny bud that receives signals from neighboring cells.

Yasuda, an HHMI early career scientist, is a biophysicist by training. For his Ph.D. dissertation, he developed ways to image single molecules tethered to glass slides. To better understand the molecular intricacies of learning, memory, and behavior, he has shifted his interests to imaging molecules in single synapses in brain slices. Hundreds of molecules are needed to transform a discrete event into a long-lasting memory, and in his latest study, his team reports exactly when and where in the neuron two important molecules are active.

“The synapse is small but not simple,” Yasuda says. “It’s got a lot of complicated machinery, and it’s the perfect place to use my biophysical background.”

When one neuron fires to another, the synapse between the cells changes in strength—a process called synaptic plasticity. Changes lasting minutes or longer are thought to encode long-term memories. In particular, the receiving neuron goes through many changes as receptors and other proteins shuttle to its spines. Scientists have had trouble figuring out how each of the many molecular players behaves in relation to the others, in both space and time. Yasuda’s been particularly interested in finding the molecules responsible for turning short-term events into longer-term cell changes.

Image: Yasuda lab

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