Sea Slugs Learn Through RNA-Supported Habituation, Study Finds

By studying sea slugs in the lab, researchers have deciphered how changes in molecules called transfer RNAs (tRNAs) accompany the remodeling of synapses and behavioral habituation, an elemental form of learning. "Together, our findings reveal that neuronal tRNA modifications are reprogrammed during a learning paradigm, raising new, testable questions about the molecular mechanisms underlying behavioral habituation," Han Huang and colleagues write. tRNA is a common type of RNA that frequently becomes modified, especially in response to environmental cues. Prior research suggests that modifications in tRNAs play central roles in learning and memory, but they are difficult to isolate and study in the intricate mammalian nervous system. Instead, Huang et al. turned to the humble sea slug species Aplysia californica, which is a popular model organism for neurobiology research. Despite their simple nature, these animals show many forms of learning such as behavioral habituation, which occurs when an organism gradually responds less to an applied stimulus. The researchers gently spritzed water on the slugs' siphons to produce a defensive withdrawal reflex, and studied the mollusk's nervous systems as they became habituated to the stimulus. Dozens of tRNAs underwent structural modifications as the slugs became habituated, including a rise in the abundance of an amino acid modification named N6-­isopentenyladenosine. Notably, these shifts occurred even though the expression of the tRNAs themselves remained constant, suggesting that habituation instead altered the activity of enzymes that modify tRNAs. Huang et al. also observed some unexpected changes in the abundance of small RNA modifications related to feeding in habituated slugs. They speculate that these findings could be related to behavioral patterns in marine mollusks, which suppress feeding behavior in response to aversive stimuli that might hint at the presence of predators.