Cerebellar noradrenergic inhibition and the vestibulo-ocular reflex in goldfish (Carassius auratus)

Vestibulo-ocular reflex adaptation has served as a model system for investigating neuroplasticity within the sensori-motor system. Clear vision is maintained, with the aid of this reflex, during head movements by generating eye movements that are equal in velocity and opposite in direction to that of the head. A mismatch of visual and vestibular stimulation results in a progressive adaptive change in the reflex and image slip is eliminated. The three neuron vestibulo-ocular reflex arc is simple and has been conserved across species. Vestibular signals are sent via side chain into the cerebellum where adaptation takes place. Though it is a simple model, the vestibulo-ocular reflex has been used extensively for studying sensori-motor neuroplasticity.; Depletion of norepinephrine has been shown to interfere with neuroplastic processes in the central nervous system (i.e. visual cortex, cerebellar long term depression, hippocampal long term potentiation). No other work has determined which adrenergic receptor subtype or mechanism produced the effects seen in these experiments. Norepinephrine and its receptor subtypes have been localized in the cerebellum, one of two areas responsible for the VOR adaptation.; The studies described in this thesis used VOR adaptation in Carassius auratus (goldfish) to investigate the involvement of noradrenergic pharmacology in sensori-motor plasticity. Results of these studies showed that localized vestibulo-cerebellar injection of noradrenergic receptor antagonists (propranolol, a beta1 and beta2 adrenergic receptor antagonist; ICI 118,551, beta2 adrenergic receptor antagonist; and atenolol, beta1, adrenergic receptor antagonist) or SQ 22,536, adenylate cyclase inhibitor, blocked the increase modification of the vestibulo-ocular reflex. These compounds had no effect on VOR gain decrease modification. This study also showed that these compounds had no effect on the retention of previously adapted VOR gain increases or decreases.; The noradrenergic beta1 receptor acts by recruiting adenylate cyclase system in vestibulo-cerebellum neurons to produce sensori-motor plastic changes that occur in learning and memory. Thesis results suggest that long term depression, gain increase modification, and the noradrenergic system are interrelated.