Synaptic Remodeling through MAPK

Abstract

Synaptic plasticity is a model for learning and memory. Dendrites, the sites of excitatory synaptic contacts, undergo morphological changes in response to stimuli. Wu et al. investigated the role of the mitogen-activated protein kinase (MAPK) pathway in changes in dendritic structure in response to multiple brief depolarizations over a period of minutes in cultured neurons or explants. Single stimuli (depolarizations induced by elevated extracellular K + ) of long or short duration produced a transient activation of the MAPKs, ERK1 and ERK2, measured as phosphorylation of these MAPKs. However, repeated spaced depolarizations produced a prolonged MAPK phosphorylation. Application of pharmacological inhibitors showed that the initial increase in MAPK activity depended on an increase in the concentration of free intracellular Ca 2+ , activation of calmodulin and calcium/calmodulin-dependent kinase, the small guanosine triphosphatase Ras, and MEK (the upstream kinase for ERK1 and 2). Persistent MAPK phosphorylation required continuous activity of MEK and was dependent on protein kinase A. In explants of dentate gyrus transfected to express green fluorescent protein, MAPK activity was found to be essential for changes in dendrite morphology (filopodial extensions and the formation of new spines) produced by multiple spaced stimulations. G.-Y. Wu, K. Deisseroth, R.W. Tsien, Spaced stimuli stabilize MAPK pathway activation and its effects on dendritic morphology. Nature Neurosci. 4 , 151-158 (2001). [Online Journal]