Molecular Mechanism of Neuronal Plasticity: Induction and Maintenance of Long-Term Potentiation in the Hippocampus

Abstract

Recent studies have demonstrated that activation of enzymes can be observed in living cells in response to stimulation with neurotransmitters, hormones, growth factors, and so forth. Thus, the activation of enzymes was shown to be closely related to the dynamic states of various cell functions. The development of new experimental methodologies has enabled researchers to study the molecular basis of neuronal plasticity in living cells. In 1973, Bliss and his associates identified the phenomena of long-term potentiation (LTP). Since it was thought to be a model for neuronal plasticity such as learning and memory, its molecular mechanism has been extensively investigated. The mechanism was found to involve a signal transduction cascade that includes release of glutamate, activation of the NMDA glutamate receptors, Ca(2+) entry, and activations of Ca(2+)/calmodulin-dependent protein kinases (CaM kinases) II and IV and mitogen-activated protein kinase (MAPK). Consequently, AMPA glutamate receptors were activated by phosphorylation by CaM kinase II, resulting in an increase of Ca(2+) entry into postsynaptic neurons. Furthermore, activation of CaM kinase IV and MAPK increased phosphorylation of CREB (cyclic AMP response element binding protein) and expression of c-Fos by stimulation of gene expression. These results suggest that LTP induction and maintenance would be models of short- and long-term memory, respectively.