February 18, 2026

Mapping protein production in brain cells yields new insights for brain disease Scripps Research and UC San Diego scientists used a novel method to show that some memory neurons produce proteins at higher rates than others.

February 18, 2026

LA JOLLA, CA The brain's ability to carry out everything from forming memories to coordinating movement depends on its cells producing the right proteins at the right time. But directly measuring this protein production, known as translation, across different types of brain cells has been a challenge.

Now, scientists at Scripps Research and UC San Diego have developed a technology that reveals which proteins individual brain cells are generating. In a study published in Nature on February 18, 2026, the team used their method called Ribo-STAMP to create the first maps of protein production across nearly 20,000 individual cells in the mouse hippocampus, a brain region essential for learning and memory.

This gave us an entirely different angle to look at the hippocampus, and we found a lot of new and exciting things, says Scripps Research associate professor Giordano Lippi, who co-led the study. This sort of foundational work is needed to eventually understand what goes wrong at the onset of brain diseases.

We think this technology will let the field revisit whether neurological conditions including autism spectrum disorder, fragile X syndrome, and tuberous sclerosis complex are caused by defects in translation, says co-senior author and professor Gene Yeo of UC San Diego.

In all cells, DNA is first transcribed into messenger RNA (mRNA), a temporary copy of DNA that can travel to the protein-making machinery inside cells. Then, the code is translated into proteins: the molecules that perform most cellular functions. Scientists frequently measure RNA levels as a proxy for what proteins are being made in a cell. But in brain cells, there's a large disconnect between mRNA levels and proteins. Rather than being quickly turned into proteins, mRNA is often stored in the long spindly arms of neurons, produced in advance and ready when needed.

It's been difficult to measure mRNA translation in single cells, despite the field of single cell transcriptomics expanding across tissues, conditions and diseases, says Yeo. We developed this technology in hopes that it will lead to a more complete picture.

Yeo's team had previously developed Ribo-STAMP to directly measure protein production in cells. The method works by fusing a molecular editing enzyme to ribosomes the molecular machines that carry out translation. As ribosomes translate each mRNA molecule into a protein, the enzyme makes nucleotide changes to the RNA strand. Scientists can then use standard RNA sequencing to identify which RNAs were changed.

In their new work, Yeo and Lippi collaborated to apply Ribo-STAMP to the brain for the first time. Research had already shown that neurons, with arms that reach far from the cells' central nuclei, have a poor correlation between which genes are turned on at any given time and which proteins are being made.

The team focused on the hippocampus, in part because it's already well-studied and the results could be verified. But when they measured translation in nearly 20,000 individual cells in the mouse hippocampus, they observed some unexpected patterns beyond what was known.

One of the most surprising findings came from comparing two types of neurons critical for memory: CA1 and CA3 pyramidal cells. Despite their similar roles in memory circuits, CA3 neurons showed much higher rates of protein production than CA1 neurons. The findings not only reveal that the pyramidal cell types are less similar than previously believed, but they also suggest an important role for translation in how circuits in the brain coordinate memory.

This study also indicated how different mRNA molecules made from the same gene, known as isoforms, affect how much of the corresponding protein is produced. The researchers, including co-first authors Samantha Sison and Eric Kofman of UC San Diego, and Federico Zampa of Scripps Research, discovered that in hippocampal neurons, isoforms with longer regulatory regions tended to be translated into proteins at a higher rate. Understanding this link better could shed light on how variations in mRNA transcripts might contribute to disease.

Previous work has shown how changes in isoform expression strongly correlate with neurological disorders, but the reason behind that hasn't been well-understood, says Lippi. Our work suggests that if cells prefer one isoform over another, they may actually be changing protein levels.

Beyond differences between cell types, the researchers discovered that individual neurons can exist in high and low translation states, producing proteins at dramatically different rates. Neurons in the high translation state tended to make proteins involved in communication between neurons and energy production, hinting that translation states might distinguish more active neurons from quieter ones.

Yeo says that their dataset on the brain's translatome the full set of mRNAs that are translated into proteins is just the beginning of a new understanding of how healthy brain cells coordinate protein production, and what that means for disease.

In addition to Lippi, Yeo, Sison, Kofman and Zampa, authors of the study, Single cell and isoform-specific translational profiling of the mouse brain, include Su Yeun Choi, David Sievert, Sourish Mukhopadhyay, Dong Yang, Cailynn Wang, Zhengyuan Pang and Li Ye of Scripps Research; Pratibha Jagannatha, Grady Nguyen, Jack Naritomi, Chun-Yuan Chen, Orel Mizrahi, Steven Blue and Ryan Marina of UC San Diego; Asa Shin, Akanksha Khorgade and Aziz AlKhafaji of the Broad Institute of MIT and Harvard; Wenhao Jin of Sanford Laboratories; and K

LINK:	https://www.scripps.edu/news-and-events/press-room/2026/20260218-lippi...
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