by John Pastor,Virginia Tech

This large, stitched composite created from many high-magnification images shows four mRNAs localized in the neuropil, the dense mesh of synaptic connections in a layer distinct from the cell bodies, in the juvenile mouse hippocampus. mRNAs were labeled using the HiPlex RNAscope in situ hybridization assay to detect Adcy1 (green), Aco2 (magenta), Psd (cyan), and Dlg4 (yellow), and nuclei were counterstained with DAPI (blue). This technique was used to illustrate how these mRNAs naturally appear in close proximity simply because they are abundant. Credit: Shannon Farris/Virginia Tech

Scientists found that messenger RNA (mRNA) molecules that carry genetic instructions to the far reaches of neurons in the brain tend to cluster together mostly because they are abundant, not because they move in coordinated groups.

The discovery, published ineNeuro, helps explain how neurons, which have some of the longest processes of any cells in the body, manage genetic instructions long distances from where they are made.

This fundamental process is critical to supporting neuronal communication and the modifications that occur at specific cellular communication sites calledsynapsesalong the neuron that are part of the cascade of molecular signals that occur during learning and the formation of memories.

When these processes break down—as they do in conditions such as Fragile X syndrome and some forms of autism—understanding the basic rules that guide RNA localization may help scientists pinpoint where things go wrong.

"When we compared every possible pair among the mRNAs we measured—66 combinations in all—the simplest explanation fit best: abundant mRNAs simply have more chances for their signals to overlap with the others we measured," said Shannon Farris, an assistant professor at the Fralin Biomedical Research Institute at VTC and senior author of the study.

Senior author Shannon Farris (left) and first author Renesa Tarannum of the Fralin Biomedical Research Institute at VTC reported new findings in the Society for Neuroscience journal eNeuro that shed light on how messenger RNAs behave in the brain, offering clues to how neurons support learning, memory, and conditions such as Fragile X syndrome. Credit: John Pastor/Virginia Tech

"It points to a flexible system in which mRNAs drift close together by chance. The real specificity seems to happen later at the synapse, where local signals decide how those genetic instructions are used."

Some scientists have proposed that these mRNAs travel in distinct packets carrying specific combinations, while others have suggested that each message moves on its own. The new work leans toward the simpler idea that proximity mostly depends on how much of each message a cell produces.

Beyond providing a new look at basic biology, the insight helps clarify how neurons manage the messages that guide learning and memory, including processes that are disrupted inFragile X syndrome, a genetic condition in which the protein that binds many of these RNAs is missing.

The team usedsingle-molecule imagingin intact hippocampal tissue from wild-type mice to spatially map RNA messages, many of which are known to interact with a regulatory protein called FMRP. They measured the size and brightness of each glowing RNA dot and compared how often different RNAs appeared to spatially overlap.

Now that scientists have a clearer picture of how these molecules naturally arrange themselves, next steps include looking at how this system adapts during learning—and how it may go off-track in disorders that affect communication between neurons such as Fragile X syndrome.

More information Renesa Tarannum et al, Multiplexed smFISH Reveals the Spatial Organization of Neuropil Localized mRNAs Is Linked to Abundance, eNeuro (2025). DOI: 10.1523/eneuro.0184-25.2025 Journal information: eNeuro