DEFICIENT CEREBELLAR LONG-TERM DEPRESSION AND IMPAIRED MOTOR LEARNINGIN MGLUR1 MUTANT MICE

mGluR1 mutant mice are viable but show characteristic cerebellar sympt oms such as ataxic gait and intention tremor. The anatomy of the cereb ellum is not overtly disturbed. Excitatory synaptic transmission from parallel fibers (PFs) to Purkinje cells and that from climbing fibers (CFs) to Purkinje cells appear to be functional, and voltage-gated Ca2 + channels of Purkinje cells are normal. Both PF and CF synapses displ ay normal short-term synaptic plasticity to paired stimuli. By marked contrast, long-term depression (LTD) is clearly deficient and conditio ned eyeblink response is impaired. We conclude that mGluR1 is required for the induction of LTD and that the ataxic behavior and impaired ey eblink conditioning of the mGluR1 mutant mice are primarily due to def icient LTD.