Involvement of cerebellar NMDA receptors in adaptive modification of optokinetic response

Abstract

N-methyl-D-aspartate (NMDA) receptors are implicated in synaptic plasticity and learning in the hippocampus. In the cerebellar cortex, NMDA receptors are expressed in glanule cells and inhibitory interneurons, and the NMDA receptor dependent plasticity has been reported. However, physiological role of such synaptic plasticity remains to be investigated. Here we examined the role of NMDA receptors in the adaptive modification of optokinetic response (OKR adaptaion) as a model of cerebellar-dependent motor learning in mice. OKR adaptation was induced by sustained sinusoidal oscillation (0.4Hz, 6deg peak-to-peak) of a vertically striped screen around a mouse. The mutant mice deficient in NR2A/NR2C subunit failed to show the adaptive increase of OKR gain. Further, iontophoretic application of NMDA receptor antagonist (D-AP5) into the flocculus (the cerebellar cortical region implicated in the control of OKR) in wild type mice, suppressed the adaptive increase in the OKR gain. These results suggest that NMDA receptor dependent mechanisms in the cerebellar cortex are involved in motor learning. [J Physiol Sci. 2006;56 Suppl:S188]