An abnormal striatal synaptic plasticity may account for the selective neuronal vulnerability in Huntington's disease

A marked decrease in the activity of mitochondrial complex II (succinate de hydrogenase, SD) has been found in the brains of Huntington's disease (HD) patients. Here we have examined the possibility that SD inhibitors might pr oduce their toxic action by increasing corticostriatal glutamatergic transm ission. We report that SD inhibitors produce a durable augmentation of NMDA -mediated corticostriatal excitation (DANCE) in striatal spiny neurons, but not in striatal cholinergic interneurons. DANCE involves increased intrace llular calcium, activation of MAP kinase ERK and is critically dependent up on endogenous dopamine (DA) acting via D2-1ike receptors. This pathological form of corticostriatal synaptic plasticity might play a key role in the r egional and cell-type specific neuronal death observed in HD.