Dehydration's role in learning and memory

Summary

The Takeaway CSHL Professor Hiro Furukawa, postdoc Ruben Steigerwald, and colleagues have demonstrated for the first time how NMDARs distinguish calcium from magnesium. Their work provides new insights into the key molecular features of learning and memory and could have important implications for brain development and disease. How do we learn to remember? At the most fundamental level, it’s all about chemicals and electricity. Beyond their roles in diet and nutrition, calcium and magnesium work as ions, or charged particles, in the brain. Magnesium can block a channel found within brain receptors known as NMDARs. When the blockade lifts, calcium can pass through the channel. These processes enable the brain to perform essential functions, like learning and remembering. Scientists have known all of this for a while. What they couldn’t figure out was how NMDARs tell calcium from magnesium. Now, Cold Spring Harbor Laboratory (CSHL) Professor Hiro Furukawa, postdoc Rubin Steigerwald, and colleagues have found an answer that could have implications for brain development and disease. It involves water, dehydration, and a molecular cage captured across 50,000 movies. If you think back to chemistry class, you might remember that calcium and magnesium sit close together on the periodic table. They also carry the same electrical charge. That makes it hard to tell them apart. One key difference is that “magnesium attracts water more strongly than calcium,” Furukawa says. “It’s more difficult to take out water molecules surrounding magnesium than calcium.” Since the 1980s, scientists have thought this might explain why calcium passes through the NMDAR channel more easily. It made sense. However, it was impossible to observe. It took decades for imaging technology and computing power to catch up with the theory. But now, using a method called single-particle cryo-EM, Steigerwald and his colleagues have demonstrated how dehydration enables calcium to pass through the NMDAR chann...