Memory formation is one of the brain’s most fundamental and complex functions, yet the microscopic mechanisms behind it remain poorly understood. Recent research has highlighted the importance of biochemical reactions occurring at postsynaptic densities – specialized areas where neurons connect and communicate. These tiny junctions between brain cells are now thought to be crucial sites where proteins need to organize in specific ways to facilitate learning and memory formation.

A 2021 study revealed that memory-related proteins can bind together to form droplet-like structures at postsynaptic densities, which scientists believe may be fundamental to how our brains create lasting memories. However, understanding exactly how and why such complex protein arrangements form has remained a significant challenge in neuroscience.

Against this backdrop, a research team led by Researcher Vikas Pandey from the International Center for Brain Science (ICBS), Fujita Health University, Japan, has developed an innovative computational model that reproduces these intricate protein structures. Their paper, published online in Cell Reports on April 07, 2025, explores the mechanisms behind the formation of multilayered protein condensates.

The researchers focused on four proteins found at synapses, with special attention to Ca²⁺/calmodulin-dependent protein kinase II (CaMKII) – a protein particularly abundant in postsynaptic densities. Using computational modeling techniques, they simulated how these proteins interact and organize themselves under various conditions. Their model successfully reproduced the formation of the above-mentioned “droplet-inside-droplet” structures observed in earlier experiments.

Through simulations and detailed analyses of the physical forces and chemical interactions involved, the research team shed light on a process called liquid-liquid phase separation (LLPS); it involves proteins spontaneously organizing into condensates without membranes that sometimes resemble the organelles found inside cells. Crucially, the researchers found that the distinctive “droplet-inside-droplet” structure appears as a result of competitive binding between the proteins and is significantly influenced by the shape of CaMKII, specifically its high valency (number of binding sites) and short linker length.

These findings could pave the way toward a better understanding of the possible mechanisms of memory formation in humans. However, the long-term implications of this research extend well beyond basic neuroscience. Defects in synapse formation have been associated with numerous neurological and mental health conditions, including schizophrenia, autism spectrum disorders, Down syndrome, and Rett syndrome.

“Our results revealed new structure-function relationships between proteins at synapses,” said Dr. Pandey. “We hope that our findings will contribute to the development of novel therapeutic strategies for these devastating diseases.”

The project received funding from various organizations, including the Core Research for Evolutional Science and Technology (CREST), the Japan Science and Technology Agency (JST), JSPS KAKENHI, Kobayashi foundation, ISHIZUE2024 of Kyoto University, Grant-in-Aid for Scientific Research JP18H05434, and others.

References:

* Pandey, V., et al. (2025). Unraveling memory formation: A computational model reveals new insights into protein structures at synapses. Cell Reports.
* Japanese Ministry of Education, Culture, Sports, Science, and Technology (MEXT). (n.d.). Research Grants JP18H05434 and JP20K21462.

Parkinson’s disease, a neurodegenerative disorder that affects over 10 million people worldwide, has long been shrouded in mystery. While some individuals carrying pathogenic variants that increase their risk of PD go on to develop the disease, others who also carry such variants remain unaffected. A new study from Northwestern Medicine has shed light on this enigma by identifying a set of key genes that contribute to the manifestation of Parkinson’s disease.

Using modern CRISPR technology, scientists at Northwestern Medicine systematically examined every gene in the human genome, leading them to identify a group of 16 proteins called Commander complex. This complex plays an important role in delivering specific proteins to the lysosome, a part of the cell responsible for recycling waste materials and old cell parts. Previous research has found that carrying a pathogenic variant in the GBA1 gene is the greatest risk factor for developing Parkinson’s disease and dementia with Lewy bodies (DLB). However, it was unknown why some individuals who carry these variants develop PD while others do not.

The study discovered that loss-of-function variants in Commander complex genes contribute to an increase in Parkinson’s disease risk. By examining genomes from two independent cohorts, the scientists found that people with PD had more loss-of-function variants in Commander genes compared to those without the disease. This breakthrough opens the door to previously untapped drug targets for treating PD.

The study reveals that lysosomal dysfunction is a common feature of several neurodegenerative diseases, including Parkinson’s disease. The Commander complex plays an important role in maintaining lysosomal function, suggesting that drugs targeting this complex could improve the cell’s recycling system and potentially lead to new treatments for PD.

Future research will determine the extent to which the Commander complex contributes to other neurodegenerative disorders with lysosomal dysfunction. If Commander dysfunction is observed in these individuals, drugs targeting Commander could hold broader therapeutic potential for treating such disorders. In this context, Commander-targeting drugs could also complement other PD treatments, potentially leading to combinatorial therapies.

The study was published in the journal Science and was funded by a Research Program Award (R35). The findings of this research have significant implications for understanding Parkinson’s disease and developing new treatments for this complex disorder.

When the Kīlauea Volcano erupted in May 2018, an enormous amount of ash was released into the atmosphere in a plume nearly five miles high. A new study by an international team of researchers revealed that a rare and large summertime phytoplankton bloom in the North Pacific Subtropical Gyre in the summer of 2018 was prompted by ash from Kīlauea falling on the ocean surface approximately 1,200 miles west of the volcano.

The research was published recently in JGR Oceans. “The scale and duration of this bloom were both massive, and probably the largest ever reported for the North Pacific,” said David Karl, study co-author, Victor and Peggy Brandstrom Pavel Professor, and director of the Center for Microbial Oceanography: Research and Education in the University of Hawai’i (UH) at Manoa School of Ocean and Earth Science and Technology.

Despite being one of the most active volcanoes in the world with multiple eruptions in the past 40 years, volcanic ash released from Kīlauea on Hawai’i Island had not previously been linked to open ocean phytoplankton blooms. The 2018 eruption of Kīlauea was one of the largest in more than 200 years, injecting millions of cubic feet of molten lava into the waters off the Big Island of Hawai’i and releasing an estimated 50 kilotons per day of sulfur dioxide and about 77 kilotons per day of carbon dioxide into the atmosphere.

Kīlauea’s impact near and far
Previous research led by UH Manoa oceanographers showed that as lava flowed into the ocean, it warmed nutrient-rich bottom waters, making them more buoyant. The nutrient-rich deep water rising to the sunlit surface stimulated phytoplankton growth, resulting in an extensive plume of microbes offshore of Hawai’i Island.

Volcanic ash can be transported much farther distances by winds, especially during explosive eruptions that inject materials high into the atmosphere. “After the 2018 eruption, the prevailing winds transported ash particles to the west,” said Wee Cheah, study corresponding-author and Senior Lecturer in the Institute of Ocean and Earth Sciences at Universiti Malaya.

The trajectories of the ash were recorded by Earth-orbiting satellites that detect changes in the optical clarity of the atmosphere, the so-called aerosol optical depth. Depending on the density, size, and shape of the particulate matter and local atmospheric conditions, especially rainfall, the ash eventually falls out of the atmosphere and into the surface ocean.

In addition to tracking atmospheric transport of ash across the Pacific Ocean, study lead author Chun Hoe Chow, Associate Professor in the Department of Marine Environmental Informatics at the National Taiwan Ocean University, and co-authors also used satellite data to detect ocean color, an indirect measure of the presence or absence of phytoplankton, which revealed a massive bloom near the dateline.

The team conducted a comprehensive analysis of the observations and investigated physical conditions to explain both the timing and the location of the surface bloom, a feature that is not typical in this region. “The waters in the open ocean of the Pacific are nutrient depleted and the addition of volcanic ash, especially iron in the ash, and to a lesser extent other trace elements and possibly phosphate, can stimulate the growth of marine phytoplankton,” said Karl.

Carbon out, carbon in
The growth of these specialized phytoplankton produced a lot of organic matter. When the organisms die and sink to the deep ocean, a large amount of organic carbon is exported from the surface, essentially removing carbon from the upper ocean and atmosphere.

“Our estimates are that export of organic carbon may be equivalent to about half of the carbon dioxide initially released from the eruption,” said Karl. “This marine carbon dioxide sequestration is a natural process that probably occurs whenever volcanic eruptions inject ash into the atmosphere and carry that particulate matter out to sea.”

The research team is prepared to track future volcanic eruptions and their effects on phytoplankton blooms. If another major eruption occurs, they plan to deploy a research vessel to study the bloom’s development and response in real-time.