Frequency-dependent effects of glutamate antagonists on the vestibulo-ocular reflex of the cat

In the central nervous system, sensory and motor signals at different frequencies are transmitted most effectively by neural elements that have different dynamic characteristics. Dynamic differences may be due, in part, to the dynamics of neurotransmitter receptors. For example, N-methyl-D-aspartate (NMDA) receptors are thought to be a component of the "neural integrator" of the vestibulo-ocular reflex (VOR), which generates a signal proportional to eye position. We measured the effects of blockade of NMDA and AMPA/kainate receptors on the gain and phase of the VOR at frequencies between 0.1 and 8 Hz in alert cats. The competitive NMDA antagonist, APV, and the non-competitive antagonists, MK-801 and ketamine, all caused a pronounced reduction in VOR gain. Gain was more strongly attenuated at low frequencies (0.1-1 Hz) than at higher frequencies (2-8 Hz). The phase lead of the eye with respect to the head was increased up to 30 degrees. In contrast, the reduction in gain associated with drowsiness or surgical anesthesia was not frequency-dependent. Blockade of AMPA/kainate receptors by the competitive antagonists, CNQX and NBQX, reduced the gain of the VOR at all frequencies tested. We evaluated our results using a control systems model. Our data are consistent with participation of NMDA receptors in neural integration, but suggest that NMDA receptors also participate in transmission by other components of the VOR pathway, and that neural integration also employs other receptors. One possibility is that between 0.1 and 10 Hz, higher-frequency signals are transmitted primarily by AMPA/kainate receptors, and lower frequencies by NMDA receptors. This arrangement would provide a biological substrate for selective motor learning within a small frequency range.