Analysis of vertebrate eye movements following intravitreal drug injections. III. Spontaneous nystagmus is modulated by the GABAa receptor

Abstract

1. Turtle eye movements were recorded in response to horizontal motion of patterned stimuli and intravitreal injections of selective GABAergic drugs by using a contact lens search-coil technique. Similar to results from rabbit and cat, injection of picrotoxin into the turtle's eye results in a spontaneous horizontal nystagmus, with its slow-phase movement in a temporal-to-nasal direction with respect to the injected eye. In contrast, there were no prominent vertical eye movements in response to either horizontal optokinetic stimuli or drug injections. 2. Injections of bicuculline or bicuculline methyl iodide (BMI), which selectively block the GABAa receptor, had effects similar to those of picrotoxin. The GABAa agonist muscimol, on the other hand, blocked optokinetic nystagmus (OKN). Furthermore, combinations of these drugs demonstrated competitive interactions between the agonists and antagonists. 3. The threshold dose for the eye-movement effects of each drug was ascertained with the use of a radioactive calibration procedure. Tritiated inulin was injected into the vitreous. After 1 h, ocular components were assayed for radioactivity. Then, by the use of an estimate of vitreal/retinal dilution, the retinal concentrations of these threshold doses were calculated. The computed threshold retinal concentrations of the GABAa drugs were found to be in the low micromolar range. 4. These results are discussed in terms of the directionally sensitive (DS) processing which occurs in the retina, and the output of retinal DS cells to pathways involved in oculomotor control of retinal image stabilization. It is known that intravitreal application of picrotoxin makes DS retinal ganglion cells lose their selectivity for any one direction. Based on the effect of picrotoxin on OKN, it is argued that DS retinal cells provide a major input to oculomotor subsystems involved in the stabilization of gaze. Furthermore, these intravitreal drug effects on OKN are selective for GABAa drugs, suggesting that GABAa receptors play a major role in DS processing in the retina.