The Genomic Action Potential

Neurons compute in part by integrating, on a time scale of milliseconds, many synaptic inputs and generating a digital output—the “action potential” of classic electrophysiology. Recent discoveries indicate that neurons also perform a second, much slower, integration operating on a time scale of minutes or even hours. The output of this slower integration involves a pulse of gene expression which may be likened to the electrophysiological action potential. Its function, however, is not directed toward immediate transmission of a synaptic signal but rather toward the experience-dependent modification of the underlying synaptic circuitry. Commonly termed the “immediate early gene” (IEG) response, this phenomenon is often assumed to be a necessary component of a linear, deterministic cascade of memory consolidation. Critical review of the large literature describing the phenomenon, however, leads to an alternative model of IEG function in the brain. In this alternative, IEG activation is not directed at the consolidation of memories of a specific inducing event; instead, it sets the overall gain or efficiency of memory formation and directs it to circuits engaged by behaviorally significant contexts. The net result is a sharpening of the selectivity of memory formation, a recruitment of temporally correlated associations, and an ultimate enhancement of long-term memory retrieval.