Defective control and adaptation of reflex eye movements in mutant mice deficient in either the glutamate receptor delta2 subunit or Purkinje cells.
The ionotropic glutamate receptor delta2 subunit (GluRdelta2) is selectively expressed in cerebellar Purkinje cells and is implicated in long-term depression, synaptic formation and elimination. To study the effect of GluRdelta2 deficiency on motor control, we measured the vestibulo-ocular reflex (VOR) and optokinetic response (OKR) induced by sinusoidal rotation of the animal and/or the surrounding screen in two GluRdelta2 mutant mice: a GluRdelta2 knockout mouse (delta2-/-) and a lurcher mouse with a point mutation in the GluRdelta2 gene resulting in loss of all Purkinje cells. delta2-/- showed significantly higher VOR gain in the dark (VORD) than in the wild-type. In delta2-/-, the VOR gain in light was lower than that in the dark. The phase of OKR lagged more in delta2-/- than in lurcher and wild-type mice. Both mutant mice failed to change the VORD or OKR gain adaptively in response to sustained vestibular and/or visual stimulation. Basal properties of VOR and OKR changed little by lesion of the flocculus, but they changed substantially by lesion of the inferior olivary nuclei (IO). The abnormal VOR gain and OKR phase delay were clearly reduced in delta2-/- by the latter lesion. Our results indicate that failures in the GluRdelta2-dependent synaptic regulation affect motor performance more severely than loss of cerebellar cortical outputs. This study suggests that the anomalies in delta2-/- are dependent on inputs from IO and that GluRdelta2 deficiency changed properties of not only the cerebellar cortex but also the brainstem neuronal pathways controlling reflex eye movements during development.
Katoh
Akira
A
Department of Biophysics, Graduate School of Science, Kyoto University, Kyoto 606-8502, Japan.
Yoshida
Takashi
T
Himeshima
Yufuko
Y
Mishina
Masayoshi
M
Hirano
Tomoo
T
D000222:Adaptation, Physiological / Q000502:physiology; D000704:Analysis of Variance; D000818:Animals; D002531:Cerebellum / Q000473:pathology / Q000503:physiopathology; D003624:Darkness; D004307:Dose-Response Relationship, Radiation; D004585:Electrooculography / Q000379:methods; D005133:Eye Movements / Q000187:drug effects / Q000502:physiology*; D007150:Immunohistochemistry / Q000379:methods; D026901:Membrane Transport Proteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008818:Mice, Neurologic Mutants; D016571:Neural Networks, Computer; D017711:Nonlinear Dynamics; D017120:Nystagmus, Optokinetic / Q000187:drug effects / Q000502:physiology*; D010775:Photic Stimulation / Q000379:methods; D017354:Point Mutation; D011689:Purkinje Cells / Q000502:physiology*; D011725:Pyridines / Q000633:toxicity; D017470:Receptors, Glutamate / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D012027:Reflex, Vestibulo-Ocular / Q000187:drug effects / Q000502:physiology*; D012399:Rotation; D050599:Vesicular Glutamate Transport Protein 2
D026901:Membrane Transport Proteins; D011725:Pyridines; D017470:Receptors, Glutamate; C493477:Slc17a6 protein, mouse; D050599:Vesicular Glutamate Transport Protein 2; C107913:glutamate receptor delta 2; C010835:3-acetylpyridine