Together, these data argue that dysfunction within the STN is an early feature of HD that may contribute to its expression and course. At 12 months of age approximately 30% of STN neurons had been lost, as in HD. STN activity was rescued by NMDA receptor antagonism or the break down of hydrogen peroxide. STN neurons exhibited prolonged NMDA receptor-mediated synaptic currents, caused by a deficit in glutamate uptake, and elevated mitochondrial oxidant stress, which was ameliorated by NMDA receptor antagonism. At <2 and 6 months of age autonomous STN activity was impaired due to activation of K ATP channels. To explore this potential linkage, the STN was studied in BAC transgenic and Q175 knock-in mouse models of HD. In Huntington's disease (HD) action suppression is impaired, resembling the effects of STN lesioning or inactivation. The subthalamic nucleus (STN) is an element of cortico-basal ganglia-thalamo-cortical circuitry critical for action suppression.
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