Effect of Cerebellar Inactivation by Lidocaine Microdialysis on the Vestibuloocular Reflex in Goldfish

Abstract

Vestibuloocular reflex performance and adaptation were examined during vestibulocerebellar inactivation by localized lidocaine microdialysis or injection in goldfish. In the light, eye velocity perfectly compensated for head velocity (Vis-VOR) during sinusoidal yaw rotation (1/8 Hz +/- 20 degrees). In the dark, the reflex (VOR) gain was slightly reduced (gain approximately 0.8-0.9). In neither Vis-VOR nor VOR, was gain altered after 1 h of lidocaine microdialysis in the vestibulocerebellum. Before adaptation of reflex gain, the initial suppression or augmentation of Vis-VOR reflex gain produced by in-phase or out-of-phase visual-vestibular stimulation was also unaffected by cerebellar inactivation. Subsequently, 3 h of adaptive reflex training in either the in-phase or out-of-phase paradigm (acquisition phase) respectively decreased (0.30 +/- 0.09) or increased (1.60 +/- 0.08) VOR gain during artificial cerebral spinal fluid (CSF) microdialysis. However, microdialysis of lidocaine completely blocked adaptive gain changes during a 3-4 h period of continuous application. This effect was reversible because VOR gain changes were produced 1 h after lidocaine was replaced with CSF as the dialysate. After adaptive training, bilateral CSF injections (0.25 microl/side) into the vestibulocerebellum did not alter the normal retention or decay of adapted gain changes during a 3 h period in the dark (retention phase). However, injection of lidocaine into the vestibulocerebellum completely blocked retention of the adapted VOR gain returning the gain to values recorded before adaptation. In contrast to either acute or chronic surgical removal, lidocaine inactivation of the cerebellum by microdialysis did not alter either Vis-VOR and VOR behavior or interactive Vis-VOR performance over a wide range of gain extending from 0.3 to 1.4. Thus short-term VOR motor learning is a dynamic process requiring either continuous operation of brain stem cerebellar loops or, alternatively, modifiable sites within or directly influenced by the cerebellum. Our data supports the latter hypothesis, because the direct brain stem VOR pathways appear to be unaltered after cerebellar inactivation, and, hence, independent of the VOR-adapted state.

Visual awareness and the cerebellum: possible role of decorrelation control

“…One was a direct pathway with a gain that accurately matched the head-velocity input to the eye-velocity output at high (>1 Hz) frequencies. Thus, the basic gain of the VOR was not stored in the flocculus itself but in the brainstem (Luebke and Robinson, 1994;McElligott et al, 1998;Rambold et al, 2002). The second component was a leaky integrator with time constant 0.5 s, to be consistent with the observation that after cerebellar inactivation the time constant of postsaccadic drift is longer than that obtained for the plant alone (Carpenter, 1972;Robinson, 1974;Zee et al, 1981;Godaux and Vanderkelen, 1984).…”

Learning in a Simple Motor System

“…Unilateral inactivation of the lateral vestibulocerebellum in monkeys also did not abolish longterm memory in the vertical VOR (Partsalis et al 1995). However, in the goldfish, McElligott and coworkers (McElligott et al 1998) were able to completely abolish changes in gain that had been learned within the previous few hours, by infusing lidocaine into the flocculus. More recently, similar results were obtained in the monkey (Nagao and Kitazawa 2003).…”

“…Because fish are not generally in direct contact with a firm substrate and cannot move their heads, gaze stabilization in fish must rely exclusively on visual and vestibular signals reaching the oculomotor system. Goldfish have high VOR gains and excellent VOR motor learning, and have been used successfully to demonstrate storage of short-term VOR motor learning in the cerebellar cortex (McElligott et al 1998) and monocular motor learning (McElligott and Wilson 2001). The fish cerebellar circuitry exhibits some differences from mammals (Larsell 1970).…”

Stem Cells in the Adult Zebrafish Cerebellum: Initiation and Maintenance of a Novel Stem Cell Niche

“…Skin and bone were carefully removed from the dorsal cranium of juveniles older than 7 dpf and adult fish. Juvenile and adult fish were kept anesthetized in artificial fresh water CSF (McElligott et al, 1998) …”