Guy Chéron

Disabling of the oculomotor neural integrator by kainic acid injections in the prepositus-vestibular complex of the cat.

1. This study was intended to test the candidature of the prepositus‐vestibular nuclear complex for being the location of the oculomotor neural integrator (Robinsons integrator). 2. Microinjections of kainic acid (2 micrograms dissolved in 1 microliter) were made in awake cats. Injection sites were located either in the prepositus hypoglossi nucleus (p.h.), the medial vestibular nucleus (m.v.n.), the medial longitudinal fasciculus (m.l.f.) or in the magnocellular tegmental field of the reticular formation. 3. Theory predicts that a complete disabling of the neural integrator will cause (a) an exponential post‐saccadic drift whose time constant will be 0.16 s in the dark (b) a phase lead of +93 deg as the vestibulo‐ocular reflex is tested at 0.10 Hz in the dark and (c) a nearly complete abolition of the optokinetic nystagmus (o.k.n.). 4. About 1 h after a unilateral kainic acid injection in the p.h., we observed (a) a large bilateral post‐saccadic drift (time constant sometimes as low as 0.2 s) (b) a large phase lead at 0.10 Hz (range: from +69 to +98 deg) (c) an abolition of the o.k.n. control injection of phosphate buffer in the p.h. did not produce any deficit. 5. A unilateral kainic acid injection in the m.v.n. induced a nystagmus followed by signs of bilateral failure of the neural integrator similar to those observed after kainic acid injection in the p.h. 6. Injection near the mid‐line, between the two p.h. nuclei, induced a defect of the neural integrator less than that observed after kainic acid injection in either the p.h. or the m.v.n. Injection of kainic acid in the magnocellular tegmental field of the reticular formation did not produce any sign of failure of the neural integrator. No post‐saccadic drift was observed. 7. We have concluded that (a) the p.h. nucleus is involved in the integration processing, and that (b) the m.v.n. is involved either in the integration processing or in the relaying of the output of the neural integrator to the oculomotoneurones.

Differential effect of injections of kainic acid into the prepositus and the vestibular nuclei of the cat.

1. In order adequately to control eye movements, oculomotoneurones have to be supplied with both an eye‐velocity signal and an eye‐position signal. However, all the command signals of the oculomotor system are velocity signals. Nowadays, there is general agreement about the existence of a brainstem network that would convert velocity command‐signals into an eye‐position signal. This circuit, because of its function, is called the oculomotor neural integrator. The most obvious symptom of its eventual failure is a gaze‐holding deficit: in this case, saccades are followed by a centripetal post‐saccadic drift. Although the oculomotor neural integrator is central in oculomotor theory, its precise location is still a matter for debate. 2. Previously, microinjections of kainic acid (KA) into the region of the nucleus prepositus hypoglossi (NPH) and of the medial vestibular nucleus (MVN) were found to induce a horizontal gaze‐holding failure both in the cat and in the monkey. However, the relatively large volumes (1‐3 microliters) and concentrations (2‐4 micrograms microliters‐1) used in these injections made it difficult to know if the observed deficit was due to a disturbance of the NPH or of the nearby MVN. These considerations led us to inject very small amounts of kainic acid (50 nl, 0.1 microgram microliter‐1) either into the rostral part of the MVN or into different sites along the NPH of the cat. 3. The search coil technique was used to record (1) spontaneous eye movements (2) the vestibulo‐ocular reflex (VOR) induced by a constant‐velocity rotation (50 deg s‐1 for 40 s) and the optokinetic nystagmus (OKN) elicited by rotating an optokinetic drum at 30 deg s‐1 for 40 s. 4. In each injection experiment, the location of the abducens nucleus of the alert cat was mapped out by recording the antidromic field potentials evoked by the stimulation of the abducens nerve. Two micropipettes were then glued together in such a way that when the tip of the recording micropipette was in the centre of the abducens nucleus the tip of the injection micropipette was in a target area. The twin pipettes were then lowered in the brainstem until the recording micropipette reached the centre of the abducens nucleus. Kainic acid was then injected into the brainstem of the alert cat through the injection micropipette by an air pressure system. 5. Carried out according to such a protocol, KA injections into the NPH or the rostral part of the MVN consistently led to specific eye‐movement changes.(ABSTRACT TRUNCATED AT 400 WORDS)

Ketamine induces failure of the oculomotor neural integrator in the cat.

We studied the effect of intramuscular injection of low dose of ketamine (1 mg/kg) on the spontaneous ocular movements of the cat. Ketamine is a non-competitive antagonist of the N-methyl-D-aspartate (NMDA) receptors, which is used as an anesthetic agent in human surgery. We found that ketamine administration caused a failure of gaze holding: each saccade was followed by a centripetal post-saccadic drift. This defect was selective: the dynamics of the saccades was not altered (the amplitude/maximum velocity relationship was unaffected by ketamine at the dose of 1 mg/kg). We postulated that the observed effect was due to the fact that NMDA receptors were implicated in the network of the oculomotor neural integrator that converted activity related to the saccade (pulse signal) into activity responsible for gaze holding (step signal).

NMDA receptors are involved in temporal integration in the oculomotor system of the cat.

Spontaneous eye movements were recorded before and after a microinjection (0.1-0.2 microliter) of either APV (an NMDA receptor antagonist) or NBQX (a non-NMDA receptor antagonist) into the nucleus prepositus hypoglossi (NPH) of the alert cat. A unilateral injection of APV caused bilateral failure of the horizontal gaze-holding system: in the light, each saccade was followed by a post-saccadic drift. A unilateral injection of NBQX caused no sign of gaze-holding failure; in the light, spontaneous eye movements were unaffected; in complete darkness, a nystagmus with linear slow phases directed towards the injected side was observed. We conclude that NMDA receptors of the NPH neurones are involved in the gaze-holding system.

Emergence of clusters in the hidden layer of a dynamic recurrent neural network.

Abstract. The neural integrator of the oculomotor system is a privileged field for artificial neural network simulation. In this paper, we were interested in an improvement of the biologically plausible features of the Arnold-Robinson network. This improvement was done by fixing the sign of the connection weights in the network (in order to respect the biological Dales Law). We also introduced a notion of distance in the network in the form of transmission delays between its units. These modifications necessitated the introduction of a general supervisor in order to train the network to act as a leaky integrator. When examining the lateral connection weights of the hidden layer, the distribution of the weights values was found to exhibit a conspicuous structure: the high-value weights were grouped in what we call clusters. Other zones are quite flat and characterized by low-value weights. Clusters are defined as particular groups of adjoining neurons which have strong and privileged connections with another neighborhood of neurons. The clusters of the trained network are reminiscent of the small clusters or patches that have been found experimentally in the nucleus prepositus hypoglossi, where the neural integrator is located. A study was conducted to determine the conditions of emergence of these clusters in our network: they include the fixation of the weight sign, the introduction of a distance, and a convergence of the information from the hidden layer to the motoneurons. We conclude that this spontaneous emergence of clusters in artificial neural networks, performing a temporal integration, is due to computational constraints, with a restricted space of solutions. Thus, information processing could induce the emergence of iterated patterns in biological neural networks.

Gaze holding defect induced by injections of ketamine in the cat brainstem

The signal responsible for horizontal gaze holding is known to be generated, at least in part, by the prepositus hypoglossi (PH) nucleus, whereas that responsible for vertical gaze holding is known to be generated by the interstitial nucleus of Cajal (INC). An intramuscular injection of ketamine was recently demonstrated to induce a gaze holding failure. The aim of the present study was to analyse if ketamine produced this effect by acting, at least in part, on the PH nucleus. We found that a unilateral injection of a small amount of ketamine in the PH nucleus could cause either bilateral horizontal gaze holding failure or a vertical gaze holding failure or both an horizontal and a vertical gaze holding failure.

Involvement of the N-methyl-D-aspartate receptors of the vestibular nucleus in the gaze-holding system of the cat.

Eye movements were recorded in alert cats after injections into one of the medial vestibular nuclei (MVN) either of a N-methyl-D-aspartate (NMDA) antagonist or of a non-NMDA antagonist. A gaze-holding failure was caused by the NMDA antagonist when it was injected into the central part of the MVN but not when it was injected into the rostral part of that nucleus. By contrast, injections of the non-NMDA-receptor antagonist into the MVN did not cause any sign of gaze-holding failure. We conclude that the NMDA receptors located in the central part of the MVN are involved in the gaze-holding system.

Chapter 20 Behavioural analysis of Purkinje cell output from the horizontal zone of the cat flocculus

Publisher Summary This chapter describes the properties of the simple spike discharges of Purkinje cells (P-cells) located in the horizontal zone of the cat flocculus and compares the output signals with those of the flocculus projecting neurons (FPNs) in the medial vestibular nucleus (MVN), nucleus prepositus hypoglossi (NPH), and nucleus incertus (NIC). Recently, floccular functions have been analyzed by an approach based on recording in the vestibular nuclei of the floccular target neuron (FTN) and on the comparison of these FTNs with vestibular neurons that do not receive direct floccular inhibition. Another approach to the floccular function consists of the recording of the FPNs identified in different nuclei of the brainstem by antidromic activation from the flocculus. The behavior of the P-cells of the horizontal zone of the flocculus differs significantly from those of the FPNs located in the MVN, NPH, and NIC. The convergence into the horizontal zone of the cat flocculus of an input signal only related to head velocity and of other input signals combining eye velocity and eye position is one of the main factors for the emergence of the pure position P-cell behavior and the more complex head velocity plus position P-cells.

Role of the vestibular commissure in gaze-holding in the cat: a pharmacological evaluation.

Recent theoretical studies have proposed that the vestibular commissure is a major component of the horizontal gaze-holding system. In order to test this hypothesis, we injected either bicuculline, a GABA receptor antagonist, or strychnine, a glycine receptor antagonist, into the medial vestibular nucleus of alert cats. The inter- vestibular connection is indeed inhibitory and mediated by GABA and glycine. As neither bicuculline nor strychnine caused serious deficit of the gaze-holding system, we conclude that the vestibular commissure is not essential for gaze-holding.

The role of the vestibular commissure in the gaze holding of the cat

Recent theoretical studies have proposed that the vestibular commissure is a major component of the horizontal gaze-holding system. In order to test this hypothesis, we disrupted the vestibular commissure of the cat by a parasagittal cut running between an abducens nucleus and the adjacent medial vestibular nucleus. Successfully lesioned cats suffered of a characteristic syndrome. In the light, gaze holding was impaired when the animal was looking toward the side of the lesion, but normal when looking toward the opposite side. We conclude (1) that the vestibular commissure is a component of the gaze-holding system, (2) that the vestibular commissure is less essential for gaze holding than other structures as the nucleus prepositus hypoglossi, and (3) that the horizontal gaze-holding system consists of two halves, each being more active in ipsilateral than in contralateral gaze.