CEREBELLAR NITRIC-OXIDE IS NECESSARY FOR VESTIBULOOCULAR REFLEX ADAPTATION, A SENSORIMOTOR MODEL OF LEARNING

1. Nitric oxide(NO) production in the nervous system has been implicat ed in cellular mechanisms of learning and memory. Our study investigat es an in vivo sensorimotor model of learning. It demonstrates that a l ocalized vestibulocerebellar injection of the NO synthase inhibitor, L -N-G-monomethyl-arginine (L-NMMA), which specifically blocks NO produc tion, inhibited the acquisition of adaptive vestibule-ocular reflex (V OR) gain increases but not gain decreases in the goldfish. 2. Restorat ion of NO production by concomitant administration of L-arginine (the substrate for NO synthase) and L-NMMA suppressed the inhibitory effect of L-NMMA on adaptive gain increases. 3. This effect of L-NMMA was st ereospecific because injection of D-NMMA did not suppress adaptive VOR gain increases. 4. Injection of L-NMMA after VOR adaptation had no ef fect on retention, failing to alter the postadaptive recovery after a VOR gain increase. 5. In conclusion, acquisition of adaptive VOR gain increases are affected by cerebellar NO inhibition. However, because g ain decreases are not, they may involve either non-NO cerebellar or ex tracerebellar mechanisms. In addition, different processes for acquisi tion and retention of gain increases may be operating, because inhibit ion of cerebellar NO affects the acquisition but not the retention pha se.