Oscillating Purkinje neuron activity causing involuntary eye movement in a mutant mouse deficient in the glutamate receptor delta2 subunit.
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 delta2 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 delta2 mutant mouse was analyzed by comparing its motor control ability with those of the wild-type mouse and the lurcher mutant mouse, which loses all Purkinje neurons, the sole output neurons in the cerebellar cortex. Unexpectedly, the delta2 mutant mouse showed severer motor discoordination than the lurcher mouse without any cerebellar cortical outputs. The delta2 mutant mouse showed involuntary spontaneous eye movement with characteristic 10 Hz oscillation, which disappeared by ablation of the cerebellar flocculus, suggesting that the delta2 mutant cerebellar cortex outputs an abnormal signal. In vivo extracellular recordings of neuronal activity revealed that Purkinje neurons tended to fire clustered action potentials and complex spikes at approximately 10 Hz in the delta2 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 delta2 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.
Yoshida
Takashi
T
Department of Biophysics, Graduate School of Science, Kyoto University, Kyoto 606-8502, Japan.
Katoh
Akira
A
Ohtsuki
Gen
G
Mishina
Masayoshi
M
Hirano
Tomoo
T
D000200:Action Potentials; D000818:Animals; D001259:Ataxia / Q000235:genetics / Q000503:physiopathology*; D001683:Biological Clocks; D002531:Cerebellum / Q000473:pathology / Q000503:physiopathology; D020820:Dyskinesias / Q000235:genetics / Q000503:physiopathology*; D051379:Mice; D008818:Mice, Neurologic Mutants; D009475:Neurons, Afferent / Q000473:pathology / Q000502:physiology; D015835:Ocular Motility Disorders / Q000235:genetics / Q000503:physiopathology*; D018408:Patch-Clamp Techniques; D021122:Protein Subunits / Q000172:deficiency / Q000235:genetics; D011689:Purkinje Cells / Q000473:pathology / Q000502:physiology*; D017470:Receptors, Glutamate / Q000172:deficiency* / Q000235:genetics
D021122:Protein Subunits; D017470:Receptors, Glutamate; C107913:glutamate receptor delta 2