Extracellular Signal-Regulated Kinase, Synaptic Plasticity, and Memory

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Abstract
The mitogen-activated protein kinase, extracellular signal-regulated kinase (ERK), has been studied extensively in recent years for its involvement in synaptic plasticity and memory function. Activation of ERK is coupled to stimulation of cell-surface proteins via several different upstream signaling pathways, and contributes to the regulation of diverse cellular processes, ranging from cell excitability to gene expression. We herein review evidence for ERK's role in different forms of synaptic plasticity and different types of learning paradigms, drawing on examples from different systems in molluscs as well as the mammalian brain. The picture that emerges is that ERK activation in response to conditions that give rise to synaptic and behavioral modification contributes to that modification in a multitude of functionally distinct ways. The functional diversity is likely to be achieved by the operation of multiple, parallel ERK cascades that differ with respect to the subcellular compartments in which ERK exerts its effects and the temporal windows during which the effects are manifested. We conclude that our understanding of the mechanisms by which ERK contributes to synaptic plasticity and memory has much to gain by further study of the signaling events up- and downstream of ERK activation and the spatiotemporal characteristics of ERK activation in association with activity-dependent synaptic modification and information processing.