Plasticity of Long-Term Plasticity of a Single Sensorimotor Synapse

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One of the most important problems in neurobiology is how memories are maintained in the brain over the course of decades. Traditionally, it has been thought that, after induction and an initial period of consolidation, memories are relatively permanent and resistant to disruption. Recent evidence, however, indicates that long-term memories are far more labile than previously supposed. Evidence for the lability of long-term memory has come from studies in which a consolidated memory is reactivated in an animal, typically by giving the animal a stimulus that reminds it of the original learning experience. It has been found that reactivation renders a stored, long-term memory subject to disruption by manipulations, such as inhibition of protein synthesis, that disrupt newly formed memories. This finding has led to the idea that, upon reactivation, long-term memories undergo a new episode of consolidation ("reconsolidation"), during which they are fragile and subject to elimination. Although the notion that consolidated memories undergo reconsolidation following their reactivation is increasingly accepted by neurobiologists, the mechanisms of memory reconsolidation are poorly understood. This project will use a simple invertebrate organism to gain general insights into the cellular and molecular processes that mediate memory reconsolidation. A significant advantage of this model system is that memory reconsolidation can be examined at the level of a single sensorimotor synapse in dissociated cell culture. This permits rigorous mechanistic analyses of reconsolidation. Among the questions that will be addressed during the project are the extent to which disruption of reconsolidation of a memory actually eliminates the memory; the similarity between the molecular signaling processes that are involved in original memory consolidation to those involved in memory reconsolidation; and the effect of reconsolidation on the strength of the memory. The latter question will be examined on both the behavioral and synaptic levels. The broader impacts of this project include the training of underrepresented graduate students and undergraduates. In addition, significant public outreach will be undertaken.