Memory formation and the regulation of gene expression

Abstract

On a cellular level, formation of memory is based on a selective change in synaptic efficacy that is both fast and, in case of important information, long-lasting. Rapidity of cellular changes is achieved by modifying preexisting synaptic molecules (receptors, ion channels), which instantaneously alters the efficacy of synaptic transmission. Endurance, that is the formation of long-term memory (LTM), is based on transient and perhaps also long-lasting changes in protein synthesis. A number of different methods exist to interfere with the synthesis of specific proteins or proteins in general. Other methods, in turn, help to identify proteins whose synthesis is changed following learning. These mostly molecular methods are briefly described in the present review. Their successful application in a variety of memory paradigms in invertebrates and vertebrates is illustrated. The data support the importance of selective changes in gene expression for LTM. Proteins newly synthesized during memory consolidation are likely to contribute to restructuring processes at the synapse. altering the efficiency of transmission beyond the scope of STM. Increased or, less often, decreased synthesis of proteins appears during specific time windows following learning. Recent evidence supports older data suggesting that two or even more waves of protein synthesis exist during the consolidation period. It is expected that the new molecular methods will help to identify and characterize molecules whose expression changes during LTM formation even in complex vertebrate learning paradigms.

Identification of Genes Expressed in the Amygdala During the Formation of Fear Memory

“…The remaining 12 factors appear to fall into one of two major categories: factors that contribute to signal transduction pathways and factors that mediate morphological reorganization processes. This observation is in good agreement with our current knowledge of gene expression and cellular changes during the formation of LTM (Stork and Welzl 1999). In particular, the prominent induction and graded increase across behavioral groups of aldehyde reductase, a key enzyme of monoamine metabolism, suggest that metabolic control of monoamine function plays an important role in the formation of fear memory and the stress-and fear-related modulation of amygdala function.…”

“…The storage of long-term memories (LTMs) involves highly regulated and coordinated cellular and molecular changes in the central nervous system including the de novo synthesis of proteins, which are indispensable for the morphological and biochemical refinements that form a permanent memory trace (Stork and Welzl 1999). Fear memory is a particularly rapid LTM formed during an aversive experience, for example, during Pavlovian fear conditioning; it is thus highly amenable to neurochemical and electrophysiological investigation.…”

Motor-Skill Learning-Associated Gene Regulation in the Striatum: Effects of Cocaine

“…Long-term memory formation is known to be dependent on protein synthesis (Davis and Squire, 1984). Indeed, changes in gene expression related to learning have been described in many models of learning and memory (Stork and Welzl, 1999). It is thought that proteins expressed during learning allow changes in structure and efficacy of synapses thus mediating longterm memory consolidation (eg Davis and Squire, 1984;Bailey and Kandel, 1993;Bailey et al, 1996;Moser, 1999).…”

Memory-specific temporal profiles of gene expression in the hippocampus

“…STM involves posttranslational modifications of preexisting molecules that alter the efficiency of synaptic transmission. In contrast, LTM can be blocked by inhibitors of transcription or translation, indicating that it depends on de novo gene expression (2,3). Proteins that are newly synthesized during memory consolidation may contribute to restructuring processes at the synapse and thereby alter the efficiency of synaptic transmission beyond the duration of STM.…”