黑料吃瓜资源

How do we learn to remember? At the most fundamental level, it鈥檚 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鈥檛 figure out was how NMDARs tell calcium from magnesium. Now, 黑料吃瓜资源 (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 鈥渕agnesium attracts water more strongly than calcium,鈥� Furukawa says. 鈥淚t鈥檚 more difficult to take out water molecules surrounding magnesium than calcium.鈥�

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 channel.

Watch as calcium passes through the Asn cage 鈥渟electivity filter,鈥� which Hiro Furukawa likens to 鈥渁 sieve.鈥� This video shows calcium in cyan at five distinct positions from the top to the bottom of the Asn cage, as captured by single-particle cryo-EM.

Steigerwald focused his attention on a part of the channel known as the Asn cage. This molecular cage acts as a filter, allowing only molecules that are small enough to pass. Outside the filter, the team saw magnesium surrounded by water, blocking the channel. If you鈥檙e picturing a backed-up spaghetti strainer, you鈥檙e right. 鈥淚t鈥檚 a sieve,鈥� Furukawa explains.

So that covers water, dehydration, and the molecular cage. But how do 50,000 movies fit into the picture? 鈥淚t鈥檚 all about resolution,鈥� Furukawa says.

Think about water鈥檚 fluid nature. It鈥檚 constantly in motion. Tracking the movement of a few water molecules requires high resolution. Single-particle cryo-EM images get you part of the way there. But to really see what’s going on, you need to take millions of images from different angles. Therein lies the power of CSHL鈥檚 cryo-EM and high-performance computing cores. Additionally, Furukawa鈥檚 team confirmed their observations using electrophysiology.

Why go through all this trouble? Remember, we鈥檙e not just talking about chemicals. We鈥檙e viewing one of the key molecular features of learning and memory. Furthermore, the Asn cage is susceptible to spontaneous mutations linked to , which cause severe developmental disabilities. Many patients with these mutations are non-verbal and unable to walk. They often experience severe seizures. To understand the effects of these mutations, you need to know what you鈥檙e looking at. This study gives scientists the clearest picture yet.

Written by: Samuel Diamond, Senior Communications Strategist | [email protected] | 516-367-5055

Funding

National Institute of Neurological Disorders and Stroke, National Institute of Mental Health, Austin鈥檚 Purpose, Robertson Research Fund, Doug Fox Alzheimer鈥檚 Fund, Heartfelt Wings Foundation, Gertrude and Louis Feil Family Trust, German Research Foundation

Citation

Steigerwald, R.,听et al., 鈥�Molecular mechanism of calcium permeability and magnesium block in NMDA receptors鈥�,听Nature Neuroscience,听May 5, 2026. DOI:听

Core Facilites

鈥淭丑别 Electron Cryomicroscopy (Cryo-EM) Facility offers researchers access to cutting-edge technology that has made it possible to visualize complex biological systems at near atomic resolution and detail, providing novel molecular insight into human biology and disease.鈥� 鈥� Cryo-EM Facility Manager Dennis Thomas