Vestibulo-ocular reflex adaptation in cats before and after depletion of norepinephrine

The vestibulo-ocular reflex (VOR) operates to stabilize the eyes in space during movements of the head. The system has been described as having a gain of approximately -1 since stimulation of the semi-circular canals brought about by head movements will have the effect of causing the eyes to rotate an equal amount in the opposite direction. Change in the gain of the VOR has been put forth as a model to study plasticity in the central nervous system. Since numerous studies have implicated norepinephrine (NE) in neuroplasticity and modifiability of neural circuits, we attempted to determine the effect of NE depletion (via 6-hydroxydopamine (6-OHDA) intra-cisternal injection) on the modifiability of the VOR. We have found that cats increase the gain of their VOR over a four hour period when rotated in the horizontal plane in a manner equal but opposite to the rotation of a surrounding opto-kinetic drum. The entire group of animals manifests a statistically significant decrement in their ability to increase VOR gain when central stores of norepinephrine are depleted via intra-cisternal injection of 6-OHDA. Individual animals manifest a wide variety of gain changes (0.98 to 1.62). We have found that there were two groups of cats--high and low gain modifiers. The greatest reduction in VOR gain increase after NE depletion was observed in the high gain modifiers. No difference was observed in the low gain modifiers. These same animals tested for VOR modification after amphetamine injection, produced similar results. Alertness during the VOR modification task, as estimated by saccadic eye movement counts, was unchanged after NE depletion NE levels, measured by HPLC-EC, after depletion were reduced to the greatest extent in the cerebellum. There was also a substantial reduction of NE in the visual cortex with less of a reduction in the brain stem.