Oscillating Purkinje Neuron Activity Causing Involuntary Eye Movement in a Mutant Mouse Deficient in the Glutamate Receptor δ2 Subunit

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Abstract
How failures in regulation of synaptic transmission in the mammalian CNS affect neuronal activity and disturb motor coordination is addressed. The mutant mouse deficient in the glutamate receptor δ2 subunit, specifically expressed in cerebellar Purkinje neurons, has defects in synaptic regulations such as synaptic plasticity, stabilization, and elimination of synaptic connections and shows failures in motor coordination and learning. In this study, the cause of motor discoordination of the δ2 mutant mouse was analyzed by comparing its motor control ability with those of the wild-type mouse and thelurchermutant mouse, which loses all Purkinje neurons, the sole output neurons in the cerebellar cortex. Unexpectedly, the δ2 mutant mouse showed severer motor discoordination than thelurchermouse without any cerebellar cortical outputs. The δ2 mutant mouse showed involuntary spontaneous eye movement with characteristic 10 Hz oscillation, which disappeared by ablation of the cerebellar flocculus, suggesting that the δ2 mutant cerebellar cortex outputs an abnormal signal.In vivoextracellular recordings of neuronal activity revealed that Purkinje neurons tended to fire clustered action potentials and complex spikes at ∼10 Hz in the δ2 mutant mouse. A whole-cell patch-clamp recording from Purkinje neurons in cerebellar slices indicated that the clustered action potentials could be induced by climbing fiber activation. Taken together, our results suggest that the δ2 subunit deficiency produces the oscillating activity in Purkinje neurons by enhancing climbing fiber inputs, causing surplus movement and affecting motor control worse than no signal at all.