Effect of muscimol microinjections into the prepositus hypoglossi and the medial vestibular nuclei on cat eye movements

Abstract

1. For horizontal eye movements, previous observations led to the hypothesis that the legendary neural integrator necessary for correct gaze holding, adequate vestibuloocular reflex (VOR), and optokinetic nystagmus, was located in the region of the complex formed by the nucleus prepositus hypoglossi (NPH) and the medial vestibular nucleus (MVN). 2. The aim of the present study was to test the respective contributions of the NPH, of the rostral part of the MVN, which contains most second-order vestibular neurons, and of the central part of the MVN to the horizontal integrator. 3. An injection of muscimol was used to inactivate each of these three zones in the cat's brain. Muscimol is a gamma-aminobutyric acid (GABA) agonist. By binding to GABAA receptors, it induces a hyperpolarization of the neurons that nullifies their activity. Muscimol was injected into the brain stem of the alert cat through a micropipette by an air pressure system. 4. The search coil technique was used to record spontaneous eye movements and the VOR induced by rotating a turntable at a constant velocity. VOR was analyzed by a new method: transient analysis of vestibular nystagmus. 5. A unilateral injection of muscimol into the NPH induced a bilateral gaze-holding failure: saccades were followed by a centripetal postsaccadic drift. A vestibular imbalance was also present but it was moderate and variable. The VOR responses were distorted drastically. Through transient analysis of vestibular nystagmus, that distortion was revealed to be due more to a failure of the neural integrator than to an alteration of the vestibular input to the neural integrator. The responses to a rotation either toward the injected side or in the opposite direction were asymmetrical. The direction of that asymmetry was variable. 6. A unilateral injection of muscimol into the rostral part of the MVN caused a vestibular imbalance: in complete darkness, a nystagmus appeared, whose linear slow phases were directed toward the side of injection. 7. A unilateral injection of muscimol into the central part of the MVN induced a syndrome where a severe bilateral gaze-holding failure was combined with a vestibular imbalance. In the light, saccades were followed by a bilateral centripetal postsaccadic drift. In complete darkness, a nystagmus was observed, whose curved slow phases were directed towards the side of injection. The VOR responses were distorted drastically. Here again, that distortion was revealed by our analysis to be due more to a failure of the neural integrator than to an alteration of the vestibular input to the neural integrator.(ABSTRACT TRUNCATED AT 400 WORDS)

The hypothesis of the uniqueness of the oculomotor neural integrator: direct experimental evidence in the cat.

“…However, the eyes drifted back toward the primary position with a longer time constant (about 1P4 s) than after a NPH lesion (Robinson, 1974;Godaux & Vanderkelen, 1984). In addition to a gaze-holding failure, lesions of the NPH (Cheron et al 1986 b), and its inactivation by muscimol microinjections (Mettens et al 1994), also induced VOR abnormalities consistent with a loss of the eye-position signal. This favours the hypothesis of a common neural integrator, since a brain lesion inducing abnormality of one ocular subsystem while sparing another subsystem would have ruled out the existence of such a common integrator.…”

“…That first hypothesis of Robinson, concerning the existence of an oculomotor integrator, has been proved experimentally. The major part of the oculomotor neural integrator(s) has (have) been located in the nucleus prepositus hypoglossi (NPH) for horizontal movements (Cheron, Godaux, Laune & Vanderkelen, 1986 b;Cannon & Robinson, 1987;Cheron, Mettens & Godaux, 1992;Mettens, Godaux, Cheron & Galiana, 1994) and in the interstitial nucleus of Cajal for vertical movements (Fukushima, 1987;Crawford, Cadera & Vilis, 1991) and for torsional movements (Crawford et al 1991).…”

“…Following lesions experimentally induced in the NPH, the cat was no longer able to maintain an eccentric position in its gaze. After each saccade, a centripetal exponential drift with a time constant of about 0-16 s was observed (Cheron et al 1986b;Cheron et al 1992;Mettens et al 1994). After cerebellectomy, the cat could not maintain its eyes in an eccentric position either.…”

Oscillatory and Intrinsic Membrane Properties of Guinea Pig Nucleus Prepositus Hypoglossi Neurons In Vitro

“…It uses eye-velocity-coded saccadic commands and head-velocity vestibular signals to generate eye-position commands (Fukushima and Kaneko 1995;Moschovakis 1997). For the horizontal plane, the prepositus hypoglossi nucleus (PHN) is the principal structure of the oculomotor integrator (Mettens et al 1994) as shown by comparison among network modeling and pharmacological for lesion experiments (Arnold et al 1999;Cannon and Robinson 1987;Chéron and Godaux 1987;Robinson 1975;Skavenski and Robinson 1973). The PHN is in the rostral medulla (McCrea and Horn 2005), near the medial vestibular nucleus (MVN), which is one of its major inputs.…”

Linear Regression of Eye Velocity on Eye Position and Head Velocity Suggests a Common Oculomotor Neural Integrator

“…For this procedure, the only difference between analyzing VOR and fixation data is the presence or absence of a non-zero head-velocity term in the oculomotor integrator equation. In the DISCUSSION, we compare this method to other methods (Mettens et al 1994;Rey and Galiana 1993;Schneider et al 2000) developed to fit eye data from an animal with an imperfector integrator performing saccades.…”