New Study Reveals Water's Unexpected Function in Brain Memory and Learning Processes

A microscopic gate inside the brain may hold the secret to how humans learn, remember, and even develop certain neurological disorders. Scientists have now captured the clearest view yet of how brain cells distinguish between two nearly identical minerals, calcium and magnesium, during the process that powers memory formation.

Researchers at Cold Spring Harbor Laboratory discovered how specialized brain receptors known as NMDARs selectively allow calcium to pass while blocking magnesium, a process essential for learning and memory.

At the center of the discovery is a tiny molecular structure called the “Asn cage,” which acts like a microscopic sieve inside the NMDAR channel. Both calcium and magnesium carry the same electrical charge and are chemically similar, making them difficult for the brain to distinguish. But the researchers found one critical difference: magnesium clings much more tightly to surrounding water molecules than does.

Using advanced single-particle cryo-electron microscopy, scientists recorded nearly 50,000 molecular “movies” to observe this process in unprecedented detail. The images revealed that magnesium, still wrapped in water molecules, becomes trapped outside the channel like debris caught in a strainer. Calcium, however, sheds its surrounding water more easily, allowing it to pass through the channel and activate crucial brain signaling pathways.

The discovery solves a scientific mystery that researchers have debated since the 1980s. Earlier theories suggested dehydration played a role in calcium transport, but technology at the time could not directly visualize the process. Advances in imaging and high-performance computing finally made it possible to observe the molecular interactions in real time.

Scientists say understanding exactly how these molecular gates function could eventually help researchers develop targeted treatments for neurological disorders linked to abnormal brain signaling.

REFERENCE: Steigerwald, R., et al. (2026). Molecular mechanism of calcium permeability and magnesium block in NMDA receptors. Nature Neuroscience. DOI: 10.1038/s41593-026-02283-3. https://www.nature.com/articles/s41593-026-02283-3