Unlocking the Memory Vault: Dopamine, Novelty, and Memory Consolidation in the Hippocampus

Most everyday memories, including numerous episodic memories formed automatically in the hippocampus, are forgotten. However, some memories are retained for extended periods through a memory stabilization process known as cellular or initial memory consolidation. Notably, in both animals and humans, the retention of everyday memories is enhanced during novel experiences occurring shortly before or after memory encoding, a process known as synaptic tagging and capture (STC). A growing body of evidence suggests that dopamine signaling via D1/D5 receptors in the hippocampus is crucial for the persistence of synaptic plasticity and memory, highlighting its significant role in novelty-associated memory enhancement. This chapter presents an overview of key findings related to the persistence of synaptic plasticity and memory in the hippocampus through hippocampal D1/D5 receptor dependency, with special emphasis on the emerging role of the locus coeruleus (LC) in novelty-associated dopamine-dependent memory consolidation. Furthermore, two distinct dopaminergic systems are explored (the ventral tegmental area (VTA)-hippocampal and LC-hippocampal systems), and the specialization mechanisms of each system in different memory consolidation processes are discussed. Additionally, the anatomical and molecular foundations of D1/D5 receptor-mediated signaling in the LC-hippocampal system are examined. Finally, the molecular mechanisms possibly underlying distinct novelty-associated memory enhancement are discussed, including the involvement of plasticity-related proteins (PRPs) in the stabilization of structural and functional changes at potentiated synapses, culminating in initial memory consolidation in the hippocampus.