Major Clue in Long-term Memory Making

Photo: Image shows the formation of dendritic spines

Image shows the formation of den-
dritic spines during long-term poten-
tiation in a single synapse. Signalling
activity is colour coded (red = high
activity of Cdc42, blue = low activity).
Activity is high only in the growing
spine, and this shows Cdc42 helps to
strengthen a synapse for long-term
memory storage; © Ryohei Yasuda,
Duke University Medical Center

Researchers have found a cascade of signalling molecules that allows a usually very brief signal to last for tens of minutes, providing the brain framework for stronger connections (synapses) that can summon a memory for a period of months or even years.

Their findings about how the synapses change the strength of connections could have a bearing on Alzheimer's disease, autism and mental retardation, said Doctor Ryohei Yasuda, assistant professor of neurobiology and senior author. "We found that a biochemical process that lasts a long time is what causes memory storage," said Yasuda.”

The researchers were investigating the signalling molecules that regulate the actin cytoskeleton, which serves as the structural framework of synapses.

"The signalling molecules could help to rearrange the framework, and give more volume and strength to the synapses," Yasuda said. "We reasoned that a long-lasting memory could possibly come from changes in the building block assemblies."

The Duke researchers knew that long-term potentiation, a long-lasting set of electrical impulses in nerve cells, is triggered by a transient increase of calcium (Ca2+) ions in a synapse. They devised experiments to learn exactly how the short Ca2+ signal, which lasts only for ~0.1s, is translated into long-lasting (more than an hour) change in synaptic transmission.

The team used a 2-photon microscopy technique to visualize molecular signalling within single synapses undergoing LTP, a method developed in the Yasuda lab. This microscopy method allowed the team to monitor molecular activity in single synapses while measuring the synapses for increase in their volume and strength of the connections.

They found that signalling molecules Rho and Cdc42, regulators of the actin cytoskeleton, are activated by CaMKII, and relay a CaMKII signal into signals lasting many minutes. These long-lasting signals are important for maintaining long-lasting plasticity of synapses, the ability of the brain to change during learning or memorization.
Many mental diseases such as mental retardation and Alzheimer's disease are associated with abnormal Rho and Cdc42 signals, Yasuda said. "Thus, our finding will provide many insights into these diseases."; Source: Duke University Medical Center