Defective control and adaptation of reflex eye movements in mutant mice deficient in either the glutamate receptor δ2 subunit or Purkinje cells

The ionotropic glutamate receptor δ2 subunit (GluRδ2) is selectively expressed in cerebellar Purkinje cells and is implicated in long‐term depression, synaptic formation and elimination. To study the effect of GluRδ2 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 GluRδ2 mutant mice: a GluRδ2 knockout mouse (δ2–/–) and a lurcher mouse with a point mutation in the GluRδ2 gene resulting in loss of all Purkinje cells. δ2–/– showed significantly higher VOR gain in the dark (VORD) than in the wild‐type. In δ2–/–, the VOR gain in light was lower than that in the dark. The phase of OKR lagged more in δ2–/– 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 δ2–/– by the latter lesion. Our results indicate that failures in the GluRδ2‐dependent synaptic regulation affect motor performance more severely than loss of cerebellar cortical outputs. This study suggests that the anomalies in δ2–/– are dependent on inputs from IO and that GluRδ2 deficiency changed properties of not only the cerebellar cortex but also the brainstem neuronal pathways controlling reflex eye movements during development.