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

Excessive stimulation of glutamate receptors is believed to contribute subs tantially in determining neuronal vulnerability to ischemia. However, how t his pathological event predisposes neurons to excitotoxic insults is still largely unknown. By using electrophysiological recordings from single stria tal neurons, we demonstrate in a corticostriatal brain-slice preparation th at in vitro ischemia (glucose and oxygen deprivation) activates a complex c hain of intracellular events responsible for a dramatic and irreversible in crease in the sensitivity of striatal neurons to synaptically released glut amate. This process follows the stimulation of both N-methyl-D-aspartate an d metabotropic glutamate receptors and involves the activation of the mitog en-activated protein kinase ERK via protein kinase C. This pathological for m of synaptic plasticity might play a role in the cell type-specific neuron al vulnerability in the striatum, because it is selectively expressed in ne uronal subtypes that are highly sensitive to both acute and chronic disorde rs involving this brain area.