Disrupted motor learning and long-term synaptic plasticity in mice lacking NMDAR1 in the striatum

MT Dang, F Yokoi, HH Yin… - Proceedings of the …, 2006 - National Acad Sciences
MT Dang, F Yokoi, HH Yin, DM Lovinger, Y Wang, Y Li
Proceedings of the national academy of sciences, 2006National Acad Sciences
Much research has implicated the striatum in motor learning, but the underlying mechanisms
have not been identified. Although NMDA receptor (NMDAR)-dependent long-term
potentiation has been observed in the striatum, its involvement in motor learning remains
unclear. To examine the role of striatal NMDAR in motor learning, we created striatum-
specific NMDAR1 subunit knockout mice, analyzed the striatal anatomy and neuronal
morphology of these mice, evaluated their performance on well established motor tasks, and …
Much research has implicated the striatum in motor learning, but the underlying mechanisms have not been identified. Although NMDA receptor (NMDAR)-dependent long-term potentiation has been observed in the striatum, its involvement in motor learning remains unclear. To examine the role of striatal NMDAR in motor learning, we created striatum-specific NMDAR1 subunit knockout mice, analyzed the striatal anatomy and neuronal morphology of these mice, evaluated their performance on well established motor tasks, and performed electrophysiological recordings to assay striatal NMDAR function and long-term synaptic plasticity. Our results show that deleting the NMDAR1 subunit of the NMDAR specifically in the striatum, which virtually abolished NMDAR-mediated currents, resulted in only small changes in striatal neuronal morphology but severely impaired motor learning and disrupted dorsal striatal long-term potentiation and ventral striatal long-term depression.
National Acad Sciences