Critical Role of a Nine-Amino Acid Microexon in Neuronal Memory Function in Mice

Scientists at the Center for Genomic Regulation (CRG) have uncovered a remarkable molecular mechanism underlying memory in mice. They identified a tiny, nine-amino acid segment called a microexon that is inserted solely into the DAAM1 protein within neurons. This microexon is essential for proper neuronal development, influencing the formation of synaptic structures necessary for learning and memory. When the microexon was removed in mice, the animals appeared healthy at birth, but their adult brain cells exhibited a significant reduction—about 50%—in neural spines, which are crucial for learning and memory recall.

This reduction in spines led to measurable deficits in memory performance; the mice demonstrated roughly 40% less ability in standard memory assessments. Despite neurons appearing morphologically normal under microscopes, their impaired communication reduced the brain's information-processing efficiency. Further experiments revealed that chemically modulating a specific signaling pathway could partially restore neuronal firing and memory function, indicating that this microexon acts as a molecular switch critical for cognitive processes.

The study emphasizes the evolutionary conservation of this microexon, which is present in sharks—organisms separated from humans by hundreds of millions of years. This conservation underscores its vital role in neuron function. Researchers also highlight that irregularities in microexon splicing are linked to neurodevelopmental disorders such as autism spectrum disorder, suggesting that microexon misregulation could contribute to learning disabilities.

While current findings provide a promising proof of concept that molecular interventions could enhance memory, the authors caution that therapeutic applications are still in early stages. Ongoing research aims to explore the presence of similar microexons in humans and their potential impact on cognition, paving the way for future treatments targeting splicing mechanisms in neurodevelopmental and neurodegenerative disorders.

Source: https://medicalxpress.com/news/2025-05-mouse-memory-hinges-letter-protein.html