Cerebellar AMPA/KA receptor antagonism by CNQX inhibits vestibuloocular reflex adaptation

Abstract

Vestibuloocular reflex (VOR) performance and adaptation have been investigated during antagonism of cerebellar AMPA/quisqualate and kainate receptors (AMPA/KA) by 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX). Injection of CNQX into the vestibulo-cerebellum of the goldfish before adaptation significantly inhibited and, at the highest dosage, completely prevented acquisition of adaptive reflex gain increases and decreases during a 3-h training period. Injection of CNQX before initiation of VOR adaptive training did not affect pre-adapted baseline performance of the reflex. Injection of CNQX, 1 to 2 h after the initiation of training did not alter the performance of adaptive gain increases that occurred before the injection. If injection of CNQX occurred at the end of adaptive training, there was an accelerated loss of the previously adapted gain changes during the retention period when the animal remained stationary in the dark. CNQX injection did not produce any permanent or long-term deficits, because goldfish could be retrained 48 h later to produce adaptive VOR gain changes similar to control animals. Thus, this work demonstrates that the AMPA/KA receptors located in the vestibulo-cerebellum of the goldfish are necessary for acquisition of short-term adaptive VOR gain increases and decreases. The deficit in adaptive capability was not the result of a deficit in performance, because CNQX did not inhibit an adaptive change that had already occurred as long as the adapting vestibular and visual stimulation continued. This adaptive performance could possibly be maintained by other glutamatergic (metabotropic) receptors located on the Purkinje cells. The retention of adapted gain increases and decreases after CNQX application was inhibited because AMPA/KA antagonism accelerated VOR gain loss after the completion of training when no vestibular or visual stimulation was present. Because the AMPA/KA receptors are located only in the molecular layer of the goldfish cerebellum, these results are, presumably, the result of AMPA/KA receptor antagonism at synapses located on the Purkinje cell dendrite tree.