TY - JOUR T1 - Activation of Metabotropic Glutamate Receptor Subtype 1/Protein Kinase C/Mitogen-Activated Protein Kinase Pathway Is Required for Postischemic Long-Term Potentiation in the Striatum JF - Molecular Pharmacology JO - Mol Pharmacol SP - 808 LP - 815 VL - 60 IS - 4 AU - Paolo Calabresi AU - Emilia Saulle AU - Girolama A. Marfia AU - Diego Centonze AU - Roseann Mulloy AU - Barbara Picconi AU - Robert A. Hipskind AU - François Conquet AU - Giorgio Bernardi Y1 - 2001/10/01 UR - http://molpharm.aspetjournals.org/content/60/4/808.abstract N2 - Excessive stimulation of glutamate receptors is believed to contribute substantially in determining neuronal vulnerability to ischemia. However, how this pathological event predisposes neurons to excitotoxic insults is still largely unknown. By using electrophysiological recordings from single striatal neurons, we demonstrate in a corticostriatal brain-slice preparation that in vitro ischemia (glucose and oxygen deprivation) activates a complex chain of intracellular events responsible for a dramatic and irreversible increase in the sensitivity of striatal neurons to synaptically released glutamate. This process follows the stimulation of bothN-methyl-d-aspartate and metabotropic glutamate receptors and involves the activation of the mitogen-activated protein kinase ERK via protein kinase C. This pathological form of synaptic plasticity might play a role in the cell type-specific neuronal vulnerability in the striatum, because it is selectively expressed in neuronal subtypes that are highly sensitive to both acute and chronic disorders involving this brain area. The American Society for Pharmacology and Experimental Therapeutics ER -