Role of protein synthesis and DNA methylation in the consolidation and maintenance of long-term memory in Aplysia

摘要

The formation of long-term memory depends on new proteins being made in the brain. These new proteins are used partly to build the new connections among neurons that essentially store the memory, and must be made within a critical period of time. Experiments on animals have found that new proteins must be made during or shortly after training to form a stable memory; if protein synthesis is blocked during this period, the memory will not be stabilized (a process also known as memory consolidation). Changes that alter the activity of genes in neurons also play essential roles in memory consolidation. One such change involves the attachment of a methyl group – a molecule that contains one carbon atom surrounded by three hydrogen atoms – to the DNA of a gene. This process, called DNA methylation, typically inhibits the activity of the gene. Pearce et al. looked at how completely preventing protein synthesis and DNA methylation disrupted memory consolidation in a type of marine snail called Aplysia. Previously, researchers have exploited this animal’s simple nervous system and behavior to discover basic biological mechanisms of memory that are common to all animals. The snails were given training that increased the likelihood that they would reflexively withdraw part of their body (called the siphon) in response to touch. When Pearce et al. inhibited protein synthesis soon after training, the snails did not remember the training when tested 24 hours later, as expected. Further analysis showed, however, that a trace of the memory, referred to as the “priming trace”, remained. Snails that had this priming trace could form a long-term memory after partial training, whereas untrained snails did not form memories after such partial training. Inhibiting the synthesis of proteins during the original training blocked the priming trace, as did inhibiting DNA methylation during or after training. Moreover, inhibiting DNA methylation erased a previously established memory and prevented it from being reinstated by partial training. Overall, the findings of Pearce et al. show that proteins produced in the brain by learning have multiple roles. In addition, both the consolidation and maintenance of long-term memory depend on one or more genes that otherwise suppress memory being inhibited via DNA methylation. Future work will now aim to identify the priming trace and the genes that suppress memory. Knowledge of the priming trace could lead to new treatments for memory-related disorders such as Alzheimer’s disease. Furthermore, identifying genes that can suppress memory might allow us to reduce some of the harmful effects of traumatic experience.