The role of protein synthesis in memory consolidation: Progress amid decades of debate

• Published in: Neurobiology of learning and memory Vol. 89; no. 3; pp. 293 - 311
• Main Authors: Hernandez, Pepe J., Abel, Ted
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.03.2008; Elsevier BV
• Subjects: Amnesia; Amnesia - chemically induced; Apoptosis - drug effects; cAMP; Consolidation; CREB; Cyclic AMP Response Element-Binding Protein - drug effects; Gene expression; Gene Expression - genetics; Hippocampus; Hippocampus - drug effects; Humans; Knockout; Learning; Long-Term Potentiation - drug effects; LTP; Memory; Memory - drug effects; Molecular biology; Neurology; NMDA; Post-translational modification; Protein Biosynthesis - drug effects; Protein synthesis; Protein synthesis inhibitor; Protein Synthesis Inhibitors - adverse effects; Protein Synthesis Inhibitors - pharmacology; Receptors, N-Methyl-D-Aspartate - drug effects; Reconsolidation; Rescue; Retention (Psychology) - drug effects; RNA synthesis; Side effects; Sleep; Synaptic; Systems; Tagging; Theory; Transcription; Translation; Post-translational modification; Rescue; Translation; Synaptic; Transcription; Memory; LTP; Gene expression; cAMP; Knockout; Systems; Learning; Reconsolidation; Side effects; Consolidation; Sleep; CREB; Protein synthesis; RNA synthesis; NMDA; Tagging; Amnesia; Protein synthesis inhibitor; Hippocampus
• ISSN: 1074-7427; 1095-9564
• DOI: 10.1016/j.nlm.2007.09.010

A major component of consolidation theory holds that protein synthesis is required to produce the synaptic modification needed for long-term memory storage. Protein synthesis inhibitors have played a pivotal role in the development of this theory. However, these commonly used drugs have unintended effects that have prompted some to reevaluate the role of protein synthesis in memory consolidation. Here we review the role of protein synthesis in memory formation as proposed by consolidation theory calling special attention to the controversy involving the non-specific effects of a group of protein synthesis inhibitors commonly used to study memory formation in vivo. We argue that molecular and genetic approaches that were subsequently applied to the problem of memory formation confirm the results of less selective pharmacological studies. Thus, to a certain extent, the debate over the role of protein synthesis in memory based on interpretational difficulties inherent to the use of protein synthesis inhibitors may be somewhat moot. We conclude by presenting avenues of research we believe will best provide answers to both long-standing and more recent questions facing field of learning and memory.