Anatomical evidence of the projection of pontine omnipause neurons to midbrain regions controlling vertical eye movements

Both anatomical and physiological studies have shown that pause neurons (PNs) in the medial pontine reticular formation project to two groups of burst neurons (BNs) involved in the genesis of horizontal saccadic eye movements: The excitatory burst neurons (EBNs), which lie rostral to the abducens nucleus, and the inhibitory burst neurons (IBNs), which lie caudal to the abducens. This study is concerned with the projection from PNs to a group of vertical BNs in the nucleus of the H field of Forel (H FF) in the caudomedial subthalamus. Three anatomical methods were used to demonstrate this connection. First, intra-axonal horseradish peroxidase (HRP) injection into physiologically identified PN axons demonstrated axonal branching and axonal terminations in and around the H FF. Second, micro-injection of the tracer Phaseolus vulgaris leucoagglutinin (PHA-L) into the pontine PN region labelled terminal axons and boutons in the nucleus of the H FF. Third, extracellular pressure injection of HRP into H FF yielded retrogradely labelled pontine PN neurons. These anatomical results confirmed the termination of PNs in areas controlling rapid vertical eye movements as physiologically demonstrated by Nakao et al.: Exp. Brain Res. 70:632-636, '88). This work points to the major role of pontine PNs in the synchronization of BN activity in rapid eye movements in all directions.     

Morphology of physiologically identified second-order vestibular neurons in cat, with intracellularly injected HRP

The morphology of horizontal canal second-order type I neurons was investigated by intracellular staining with horseradish peroxidase (HRP) and three-dimensional reconstruction of the cell bodies and axons. Axons penetrated in and around the abducens nucleus were identified as originating from type I neurons by their characteristic firing pattern to horizontal rotation and by their monosynaptic response to stimulation of the ipsilateral vestibular nerve. A total of 47 type I neurons were stained. The cell bodies were located in the rostral portion of the medial vestibular nucleus (MVN) and were large or medium sized and had rather elongated shapes and rich dendritic arborizations. The neurons were divided into two groups: those which projected to the contralateral side of the brain stem (type Ic neurons) and those which projected to the ipsilateral side of the brainstem (type Ii neurons). All stem axons of type Ic neurons crossed the midline and bifurcated into rostral and caudal branches in the contralateral medial longitudinal fasciculus (MLF). Two or three collaterals arising close to this bifurcation distributed terminals in a relatively wide area in the contralateral abducens nucleus. Some of these collaterals projected further to the contralateral MVN and thus are vestibular commissural axons. Some of the rostral and caudal stem axons had collaterals which projected to the contralateral nucleus prepositus hypoglossi (PH), nucleus raphe pontis, or medullary reticular formation. There were at least six classes of type Ii neurons, most of which distributed to a relatively limited region in the ipsilateral abducens nucleus and they were categorized according to their future projections into the following categories: A) no further collaterals beyond the abducens nucleus; B) collaterals in the abducens nucleus and a branch descending and terminating in ipsilateral PH; C) projected to the abducens nucleus, PH, and an area rostral to the abducens nucleus; D) projected to the abducens nucleus and to ipsilateral reticular formation rostral and caudal to the abducens nucleus; E) collaterals in the abducens nucleus and a thick caudal stem axon entering and descending in ipsilateral MLF; F) a thick caudal stem axon entering and descending in ipsilateral MLF and no collaterals to the abducens nucleus. Some type Ii neurons also had recurrent collaterals which projected back to the ipsilateral MVN; these may inhibit type II neurons during ipsilateral rotation.     

Anatomical and physiological characteristics of vestibular neurons mediating the horizontal vestibulo-ocular reflex of the squirrel monkey

The anatomical characteristics of vestibular neurons, which are involved in controlling the horizontal vestibulo-ocular reflex, were studied by injecting horseradish peroxidase (HRP) into neurons whose response during spontaneous eye movements had been characterized in alert squirrel monkeys. Most of the vestibular neurons injected with HRP that had axons projecting to the abducens nucleus or the medial rectus subdivision of the oculomotor nucleus had discharge rates related to eye position and eye velocity. Three morphological types of cells were injected whose firing rates were related to horizontal eye movements. Two of the cell types were located in the ventral lateral vestibular nucleus and the ventral part of the medial vestibular nucleus (MV). These vestibular neurons could be activated at monosynaptic latencies following electrical stimulation of the vestibular nerve; increased their firing rate when the eye moved in the direction contralateral to the soma; had tonic firing rates that increased when the eye was held in contralateral positions; and had a pause in their firing rate during saccadic eye movements in the ipsilateral or vertical directions. Eleven of the above cells had axons that arborized exclusively on the contralateral side of the brainstem, terminating in the contralateral abducens nucleus, the dorsal paramedian pontine reticular formation, the prepositus nucleus, medial vestibular nucleus, dorsal medullary reticular formation, caudal interstitial nucleus of the medial longitudinal fasciculus, and raphé obscurus. Eight of the cells had axons that projected rostrally in the ascending tract of Deiters and arborized exclusively on the ipsilateral side of the brainstem, terminating in the ipsilateral medial rectus subdivision of the oculomotor nucleus and, in some cases, the dorsal paramedian pontine reticular formation or the caudal interstitial nucleus of the medial longitudinal fasciculus. Two MV neurons were injected that had discharge rates related to ipsilateral eye position, generated bursts of spikes during saccades in the ipsilateral direction, and paused during saccades in the contralateral direction. The axons of those cells arborized ipsilaterally, and terminated in the ipsilateral abducens nucleus, MV, prepositus nucleus, and the dorsal medullary reticular formation. The morphology of vestibular neurons that projected to the abducens nucleus whose discharge rate was not related to eye movements, or was related primarily to vertical eye movements, is also briefly presented.     

Peripheral and central oculomotor organization in the goldfish, Carassius auratus

Peripheral and central oculomotor organization was studied in the goldfish. The sizes of the extraocular muscles were quantified by counting the fibers contained in a given muscle and by area measurements of the cross-sectional surfaces. All the muscles were of approximately similar size. Kinematics were determined by electrical stimulation of a given muscle. The macroscopic appearance and kinematics of the muscles had the characteristics of other lateral-eyed animals (e.g., rabbit). Locations of extraocular motor neurons were found by retrograde transport of horseradish peroxidase (HRP) following injections into individual extraocular muscles. The eye muscles were innervated by four ipsilateral (lateral rectus, medial rectus, inferior oblique, inferior rectus) and two contralateral (superior rectus, superior oblique) motor neuron pools. The oculomotor nucleus was found in the midbrain, at the level of the caudal zone of the inferior lobe of the hypothalamus. Inferior rectus motor neurons were located rostrally in the oculomotor nucleus, whereas medial rectus, superior rectus, and inferior oblique motor neurons were intermingled in its more caudal portions. All labelled cells were located dorsally and medially to the medial longitudinal fasciculus (MLF) in close proximity to either the floor of the ventricle or the midline region. Occasionally, motor neurons were interspersed within the fiber bundles of the MLF or the exiting fibers of the oculomotor nerve. The trochlear nucleus, containing superior oblique motor neurons, was found in the immediate lateral and caudal neighborhood of the oculomotor nucleus, where its rostral border overlapped with the caudal border of the latter. The abducens nucleus, containing lateral rectus motor neurons, was located in the posterior brainstem in the neighborhood of the vestibular nuclear complex. This nucleus was divided into a rostral and a caudal portion. The axons of ipsilaterally projecting motor neurons headed toward their respective nerve roots via the shortest possible route, as did the axons of superior rectus motor neurons, which crossed the midline without detour to enter the contralateral oculomotor nerve. In contrast, trochlear motor neuron axons arched around the dorsal aspect of the ventricle through the cerebellar commissure to reach the contralateral trochlear nerve. The morphology of individual motor neurons was visualized by intrasomatic injection of HRP. Cell somata had oblong shapes, and their large dendrites were oriented laterally and ventrally. The axons did not collateralize within the midbrain region or the oculomotor nerve as far as they could be traced.(ABSTRACT TRUNCATED AT 400 WORDS)     

Afferents to the abducens nucleus in the monkey and cat

The abducens nucleus is a central coordinating element in the generation of conjugate horizontal eye movements. As such, it should receive and combine information relevant to visual fixation, saccadic eye movements, and smooth eye movements evoked by vestibular and visual stimuli. To reveal possible sources of these signals, we retrogradely labeled the afferents to the abducens nucleus by electrophoretically injecting horseradish peroxidase into an abducens nucleus in four monkeys and two cats. The histologic material was processed by the tetramethyl benzidine (TMB) method of Mesulam. In both species the largest source of afferents to the abducens nucleus was bilateral projections from the ventrolateral vestibular nucleus and the rostral pole of the medial vestibular nucleus. Scattered neurons were also labeled in the middle and caudal levels of the medial vestibular nucleus. Large numbers of neurons were labeled in the ventral margin of the nucleus prepositus hypoglossi in the cat and in the common margin of the nucleus prepositus and the medial vestibular nucleus in the monkey, a region we call the marginal zone. Substantial numbers of retrogradely labeled neurons were found in the dorsomedial pontine reticular formation both caudal and rostral to the abducens nuclei. In the monkey, large numbers of labeled neurons were present in the contralateral medial rectus subdivision of the oculomotor complex, while smaller numbers occurred in the ipsilateral medial rectus subdivision and elsewhere in the oculomotor complex. In the cat, large numbers of retrogradely labeled cells were present in a small periaqueductal gray nucleus immediately dorsal to the caudal pole of the oculomotor complex, and a few labeled neurons were also dispersed through the caudal part of the oculomotor complex. Occasional labeled neurons were present in the contralateral superior colliculus in both species. The size and distribution of the labeled neurons within the intermediate gray differed dramatically in the two species. In the cat, the retrogradely labeled neurons were very large and occurred predominantly in the central region of the colliculus, while in the monkey, they were small to intermediate in size and were distributed more uniformly within the middle gray. Among the afferent populations present in the monkey, but not in the cat, was a group of scattered neurons in the ipsilateral rostral interstitial nucleus of the medial longitudinal fasciculus and a denser, bilateral population in the interstitial nucleus of Cajal.(ABSTRACT TRUNCATED AT 400 WORDS)     

Anatomical and physiological characteristics of vestibular neurons mediating the vertical vestibulo-ocular reflexes of the squirrel monkey

The morphology of 35 vestibular neurons whose firing rate was related to vertical eye movements was studied by injection of horseradish peroxidase intracellularly into physiologically identified vestibular axons in alert squirrel monkeys. The intracellularly injected cells were readily classified into four main groups. One group of cells, down position-vestibular-pause neurons (down PVPs; N = 12), increased their firing rate during downward eye positions, paused during saccades, and were located in the medial vestibular nucleus (MV) and the adjacent ventrolateral vestibular nucleus (VLV). They had axons that crossed the midline and ascended in the medial longitudinal fasciculus (MLF) to terminate in the trochlear nucleus, the lateral aspect of the caudal oculomotor nucleus, and the dorsal aspect of the rostral oculomotor nucleus. A second group of cells (N = 15) were also located in the MV and VLV, but increased their firing rate during upward eye positions, and paused during saccades. These cells had axons that crossed the midline and ascended in the contralateral MLF to terminate in the medial aspect of the oculomotor nucleus. A third group of cells (N = 4) were located in the superior vestibular nucleus, generated bursts of spikes during upward saccades, and increased their tonic firing rate during upward eye positions. These cells had axons that ascended laterally to the ipsilateral MLF to terminate in regions of the trochlear and oculomotor nuclei similar to those in which down PVPs terminated. A fourth group of cells (N = 4), located in the VLV, had axons that projected to the spinal cord, although they had firing rates that were significantly correlated with vertical eye position. Electrical stimulation of the vestibular nerve evoked spikes at monosynaptic latencies in each of the above classes of cells, six of which were injected with horseradish peroxidase. Each group of cells had collateral projections to other areas of the brainstem. Some of the neurons that projected to the contralateral trochlear and oculomotor nuclei had collaterals that crossed the midline to terminate in the oculomotor nucleus ipsilateral to the soma, and some gave rise to small collaterals that terminated in the abducens nucleus. Other areas of the brainstem that received collateral inputs from neurons projecting to oculomotor and trochlear nuclei included the interstitial nucleus of Cajal, the caudal part of the dorsal raphe nucleus, the nucleus raphe obscurus, Roller's nucleus, the intermediate and caudal interstitial nuclei of the MLF, and the nucleus prepositus.     

Afferents to the oculomotor nucleus in the goldfish (Carassius auratus) as revealed by retrograde labeling with horseradish peroxidase.

The goal of this work was to compare the distribution and morphology of neurons projecting to the oculomotor nucleus in goldfish with those previously described in other vertebrate groups. Afferent neurons were revealed by retrograde labeling with horseradish peroxidase. The tracer was electrophoretically injected into the oculomotor nucleus. The location of the injection site was determined by the antidromic field potential elicited in the oculomotor nucleus by electrical stimulation of the oculomotor nerve. Labeled axons whose trajectories could be reconstructed were restricted to the medial longitudinal fasciculus. In order of quantitative importance, the afferent areas to the oculomotor nucleus were: (1) the ipsilateral anterior nucleus and the contralateral tangential and descending nuclei of the octaval column. Furthermore, a few labeled cells were found dorsomedially to the caudal pole of the unlabeled anterior octaval nucleus; (2) the contralateral abducens nucleus. The labeled internuclear neurons were arranged in two groups within and 500 microns behind the caudal subdivision of the abducens nucleus; (3) a few labeled cells were observed in the rhombencephalic reticular formation near the abducens nucleus, most of which were contralateral to the injection site. Specifically, stained cells were found in the caudal pole of the superior reticular nucleus, throughout the medial reticular nucleus and in the rostral area of the inferior reticular nucleus; (4) eurydendroid cells of the cerebellum, located close to the contralateral eminentia granularis pars lateralis, were also labeled; and (5) a small and primarily ipsilateral group of labeled cells was located at the mesencephalic nucleus of the medial longitudinal fasciculus. The similarity in the structures projecting to the oculomotor nucleus in goldfish to those in other vertebrates suggests that the neural network involved in the oculomotor system is quite conservative throughout phylogeny. Nevertheless, in goldfish these projections appeared with some specific peculiarities, such as the cerebellar and mesencephalic afferents to the oculomotor nucleus.     

Morphology and physiology of abducens motoneurons and internuclear neurons intracellularly injected with horseradish peroxidase in alert squirrel monkeys

Axons of abducens motoneurons and internuclear neurons were penetrated with HRP-filled glass microelectrodes in alert squirrel monkeys. The firing rate of these axons and spontaneous eye movements were recorded and the axons were then injected with HRP for subsequent visualization of the recorded cells. Soma-dendritic and axon and axonal terminal morphology were studied for possible correlation with firing frequency. The physiology of squirrel monkey abducens neurons is qualitatively similar to their counterparts in the rhesus monkey and the cat, being primarily correlated with the position and velocity of the eyes. The locations of moto- and internuclear neurons are similar in the squirrel monkey and cat as are the axonal projections and terminals. However, squirrel monkey abducens cells are smaller than their feline counterparts and have dendrites that are confined to the cellular borders of the abducens nucleus. The size of the soma and proximal dendrites of moto- and internuclear neurons are poorly correlated with either their threshold for recruitment or their tonic eye position sensitivity. However, cells with smaller dendritic trees tended to have higher saccadic eye velocity sensitivity than those with larger trees. Three types of internuclear neurons were distinguishable upon the basis of their axon collaterals. All cells terminated within the medial rectus subdivision of the oculomotor nucleus. One class of cells did not give rise to collaterals before projecting to the oculomotor nucleus and the other classes gave rise to collaterals that terminated in the intermediate and/or caudal interstitial nuclei of the median longitudinal fasciculus. Within the IIIrd nucleus internuclear terminations were usually confined to a single subgroup of medial rectus motoneurons.     

The origin of brainstem afferents of the paramedian pontine reticular formation in the cat

Transcannular microinjections of horseradish peroxidase (HRP) were made into the paramedian pontine reticular formation (PPRF) in adult cats to determine the origin of the principal sources of inputs to this important preoculomotor center for the production of saccadic eye movements. Retrogradely labeled cells were observed in numerous oculomotor-related structures, including the prerubral field (rostral interstitial nucleus of the medial longitudinal fasciculus), nucleus of Darkschewitsch, nucleus of the posterior commissure, deep superior colliculus, supraoculomotor ventral periaqueductal gray, contralateral paramedian pontine reticular formation, pontine raphe and dorsal medial pontine tegmentum medial to the abducens nucleus (purported to contain omnipause neurons), cell group Y, and the perihypoglossal complex (nucleus prepositus hypoglossi). Other sources of afferents to the region included the zona incerta, lateral and medial habenular nuclei, medial hypothalamus, medial mammillary nucleus, nucleus cuneiformis, medial medullary reticular formation, and the medial and lateral cerebellar nuclei. The results are discussed in terms of the potential influence of these nuclei on the control of eye movement.     

Selective saccadic palsy caused by pontine lesions: clinical, physiological, and pathological correlations

Two patients suffered a selective deficit of voluntary saccades and quick phases of nystagmus after hypoxic-ischemic insults during open-heart surgery. All voluntary saccades, in both horizontal and vertical planes, were slow, and quick phases of vestibular and optokinetic nystagmus were absent. Smooth pursuit, the vestibuloocular reflex, the ability to hold steady eccentric gaze, and vergence eye movements were all preserved. Pathological studies in 1 patient confirmed neuronal necrosis and gliosis, consistent with ischemic lesions involving the median and paramedian pontine reticular formation and median basis pontis but sparing the rostral mesencephalon and rostral interstitial nucleus of the medial longitudinal fasciculus. These findings, taken with data from experimental studies, support the hypothesis that each functionally defined class of horizontal eye movements is controlled by a separate neural substrate that projects independently to the abducens nuclei. In addition, these data suggest that the rostral interstitial nucleus of the medial longitudinal fasciculus is dependent on inputs from the paramedian pontine reticular formation for the programming of normal vertical saccades.     

The one-and-a-half syndrome--a unilateral disorder of the pontine tegmentum: a study of 20 cases and review of the literature

The one-and-a-half syndrome is a clinical disorder of extraocular movements characterized by a conjugate horizontal gaze palsy in one direction plus an internuclear ophthalmoplegia in the other. The syndrome is usually due to a single unilateral lesion of the paramedian pontine reticular formation or the abducens nucleus on one side (causing the conjugate gaze palsy), with interruption of internuclear fibers of the ipsilateral medial longitudinal fasciculus after it has crossed the midline from its site of origin in the contralateral abducens nucleus (causing failure of adduction of the ipsilateral eye). Twenty cases are reported; 14 had multiple sclerosis.     

Update on the medial longitudinal fasciculus syndrome

Neurological Sciences - The medial longitudinal fasciculus is a key structure for conjugate horizontal eye movements by relaying signals from the abducens internuclear neurons to the medial rectus...     

Extra- and intracellular HRP analysis of the organization of extraocular motoneurons and internuclear neurons in the guinea pig and rabbit

The distribution of extraocular motoneurons and abducens and oculomotor internuclear neurons was determined in guinea pigs by injecting horseradish peroxidase (HRP) into individual extraocular muscles, the abducens nucleus, the oculomotor nucleus, and the cerebellum. Motoneurons in the oculomotor nucleus innervated the ipsilateral inferior rectus, inferior oblique, medial rectus, and the contralateral superior rectus and levator palpebrae muscles. Most motoneurons of the trochlear nucleus projected to the contralateral superior oblique muscle although a small number innervated the ipsilateral superior oblique. The abducens and accessory abducens nuclei innervated the ipsilateral rectus and retractor bulbi muscles, respectively. The somata of abducens internuclear neurons formed a cap around the lateral and ventral aspects of the abducens nucleus. The axons of these internuclear neurons terminated in the medial rectus subdivision of the contralateral oculomotor nucleus. At least two classes of guinea pig oculomotor internuclear interneurons exist. One group, located primarily ventral to the oculomotor nucleus, innervated the abducens nucleus and surrounding regions. The second group, lying mainly in the dorsal midline area of the oculomotor nucleus, projected to the cerebellum. Intracellular staining with HRP demonstrated similar soma-dendritic organization for oculomotor and trochlear motoneurons of both guinea pigs and rabbits. Dendrites of oculomotor motoneurons radiated symmetrically from the soma to cover approximately one-third of the entire nucleus, and each motoneuron sent at least one dendrite into the central gray overlying the oculomotor nucleus. In both species, a small percentage of oculomotor motoneurons possessed axon collaterals that terminated both within and outside of the nucleus. The dendrites of trochlear motoneurons extended into the medial longitudinal fasciculus and the reticular formation lateral to the nucleus. Our data on the topography of motoneurons and internuclear neurons in the guinea pig and soma-dendritic organization of motoneurons in the guinea pig and rabbit show that these species share common organizational and morphological features. In addition, comparison of these data with those from other mammals reveals that dendritic complexity (number of dendrites per motoneuron) of extraocular motoneurons exhibits a systematic increase with animal size.     

A morphological study of abducens nucleus motoneurons and internuclear neurons in the goldfish (Carassius auratus).

The location and distribution of abducens (ABD) nucleus motoneurons (Mn) and internuclear neurons (Int) were determined in the goldfish (Carassius auratus) by means of horseradish peroxidase and fluorochrome retrograde labeling. ABD Mn were labeled following tracer injection into the ipsilateral lateral rectus muscle. These Mn were arranged in two ventrolateral clusters along the rostro-caudal axis of the posterior brainstem. Both groups of neurons showed a similar number of cells, and their axons ran ventrally to their respective nerve roots. ABD Int were labeled following the injection of the tracer into the contralateral oculomotor nucleus. They also formed two distinct groups in the rostro-caudal axis. The rostral group of Int formed a dorso-lateral cap around the caudal motoneuronal pool, with little if any intermingling. The caudal group of Int was located at the same position in the dorso-ventral and medio-lateral axis as the rostral group, but 500 microns behind it. Both groups of ABD Int had a similar number of neurons. Int axons ascended dorso-medially, then crossed the midline through the internal arcuate fibers, and entered the contralateral medial longitudinal fasciculus. The soma diameters of both ABD Mn and Int were not significantly different. The relative location of both types of neurons is discussed.     

Cat medial pontine reticular neurons related to vestibular nystagmus: Firing pattern, location and projection

In alert cats, extracellular spikes of neurons in the medial pontine tegmentum were recorded simultaneously with whole nerve discharge of the abducens and medial rectus nerves horizontal vestibular nystagmus.Nystagmus-related neurons were classified by their firing patterns in relation to the abrupt cessation of the slow phase nerve activity of abducens or medial rectus nerves. The ipsilateral abducens nucleus was electrically stimulated to examine the axonal projections of physiologically identified examples of each category of neurons.Anatomically,pause units clustered near the midline at the rostral pole of the abducens nucleus.Long- andmedium-lead burst units were 1–4 mm rostral to the area for pause units. Mostburst-tonic units, clearly distinguished from nearby axons of passage, were found close to the MLF.Physiologically, it was concluded that: (1) some long-lead burst units terminate in the abducens nucleus and may excite motoneurons and/or internuclear neurons; (2) pause units directly inhibit burst inhibitory neurons which terminate slow phase activities of contralateral abducens motoneurons; (3) burst-tonic units fire in a manner very similar to contralateral abducens motoneurons; and (4) some medium-lead burst, long-lead burst and burst-tonic neurons (but not pause neurons) project to the cerebellar flocculus.     

Paresis of lateral gaze alternating with so-called posterior internuclear ophthalmoplegia. A partial paramedian pontine reticular formation-abducens nucleus syndrome

Summary A patient with multiple myeloma developed gaze paresis to the left with slowed saccades and gaze-paretic nystagmus, which alternated with abduction palsy in the left eye (with preserved oculocephalic deviation) and dissociated adducting nystagmus in the right eye, suggesting so-called posterior internuclear ophthalmoplegia. At autopsy multiple small infarcts were found with partial destruction of the left paramedian pontine reticula formation (PPRF) extending towards the abducens nucleus, which was involved only in its inferior pole. The medial longitudinal fasciculus and other oculomotor structures were spared. It is suggested that slowing of all ipsilateral saccades with gaze-paretic nystagmus corresponded to partial destruction of the PPRF, and that intermitted abduction palsy in the ipsilateral eye with adduction nystagmus in the fellow eye was due to intermittant dysfunction of the abducens nucleus. Involvement of voluntary saccades, pursuit movements and vestibulo-ocular responses may be dissociated in partial lesions of the abducens nucleus.     

Neuroanatomical identification of mesencephalic premotor neurons coordinating eyelid with upgaze in the monkey and man

Except during blinks, movements of the upper eyelid are tightly coupled to vertical eye movements. The premotor source for the coordination of lid and eye movements is unknown. The present paper provides the anatomical identification of a new premotor cell group in the rostral mesencephalon of the monkey and human, which lies in close proximity to the premotor center for vertical saccades and is thought to participate in lid-eye coordination. After injections of a retrograde transsynaptic tracer (tetanus toxin fragment C or BII(b)) into the levator palpebrae (LP), the superior rectus (SR), or the inferior oblique (IO) muscle of macaque monkeys, a small circumscribed group of premotor neurons was labeled in the central gray of the rostral mesencephalon, but not after superior oblique or inferior rectus muscle injections. This group lies immediately rostral to the interstitial nucleus of Cajal and medial to the rostral interstitial nucleus of the medial longitudinal fasciculus, each of which contain premotor neurons for vertical saccades, and was termed the M-group. Injections of tritiated leucine into the M-group led to afferent labeling primarily over LP motoneurons. In addition, label was present over the SR- and IO-motoneuron subgroups in the oculomotor nucleus and frontalis muscle motoneurons in the facial nucleus. This projection pattern of the M-group suggests a role in the coordination of the upper eyelid and eyes during upgaze. Double-labeling experiments in macaque monkeys revealed that the M-group is strongly parvalbumin immunoreactive and contains high levels of cytochrome oxidase activity. With these two histochemical markers, the homologue of the M-group was identified in the human brain as well.     

Abducens internuclear neurons and their role in conjugate horizontal gaze

Experimental evidence suggests that brain stem lesions producing paralysis of lateral gaze and dissociation of conjugate horizontal eye movements have certain common features. Both of these disturbances involve abducens internuclear neurons (Abd IN) or their projections. Attempts were made to determine the course and terminal distribution of Abd IN in the monkey by autoradiographic techniques. Tritiated amino acids injected in the abducens nucleus (Abd N) labeled: (1) root fibers ipsilaterally, and (2) fibers that ascended in medial parts of the contralateral medial longitudinal fasciculus (MLF). In the opposite oculomotor complex (OMC) silver grains were profuse over the ventral nucleus (VN, medial rectus muscle) and patchy over caudal parts of the dorsal nucleus (DN, inferior rectus muscle). Labeling of cells in the reticular formation nucleus to Abd N resulted in transport ipsilaterally, outside the MLF, to the rostral interstitial nucleus of the MLF (RiMLF), a cell group considered to be concerned with vertical eye movements. Bilateral labeling of Abd N and cells of the nucleus prepositus (NPP) resulted in bilateral: (1) transport of isotope via root fibers and the MLF, and (2) selective distribution of silver grains in the OMC. Bilateral silver grain distribution in the OMC suggested profuse terminations in VN, patchy terminations in DN and vertical, linear terminations in caudal parts of the medial nucleus (MN, superior rectus muscle). Comparisons with more discrete unilateral labeling of cells in Abd N suggested that cells of the NPP project selectively to terminations in MN, and may be related to upward eye movements. Two conclusions were drawn: (1) The paresis of ocular adduction which occurs in both anterior internuclear ophthalmophlegia and in paralysis of lateral gaze results from involvement of Abd IN or their ascending projections, and (2) the NPP appears to project selectively to parts of MN of the OMC, a cell group said to provide crossed innervation for the superior rectus muscle.     

The accessory optic system of rodents: a whole-mount HRP study

The three-dimensional fiber pathways of the accessory optic system in three species of rodents (rat, golden hamster, guinea pig) were examined on whole-mounted preparations of the diencephalon and the midbrain, without sectioning, by anterograde labeling of retinal axons with horseradish peroxidase (HRP). HRP histochemical studies on the serial coronal sections were also done. In this study, only the accessory optic system on the side contralateral to the eye injection of HRP was clearly detected. The rat accessory optic system consisted of the inferior fasciculus, the superior fasciculus, the medial terminal nucleus, the lateral terminal nucleus, and the dorsal terminal nucleus. After the inferior fasciculus arrived at the ventromedial border of the cerebral peduncle, some fibers from the inferior fasciculus ran caudally to the medial terminal nucleus. The remaining fibers from the inferior fasciculus further proceeded dorsocaudally on the surface of the cerebral peduncle and left the inferior fasciculus at various levels of the cerebral peduncle to be mixed up with the fibers from the superior faciculus. The golden hamster accessory optic system also consisted of the inferior fasciculus, the superior fasciculus, the medial terminal nucleus, the lateral terminal nucleus, and the dorsal terminal nucleus. However, all fibers of the inferior fasciculus ran caudally on the lateral surface of the hypothalamus or along the ventromedial border of the cerebral peduncle to terminate at the medial terminal nucleus. The guinea pig accessory optic system and rat accessory optic system were similar, but the posterior fibers of the superior fasciculus decreased in number, and the dorsal terminal nucleus and the posterior portion of the lateral terminal nucleus were not observed in the guinea pig accessory optic system.     

Discharge characteristics of axotomized abducens internuclear neurons in the adult cat

The aim of the present work was to characterize the axotomy-induced changes in the discharge properties of central nervous system neurons recorded in the alert behaving animal. The abducens internuclear neurons of the adult cat were the chosen model. The axons of these neurons course through the contralateral medial longitudinal fascicle and contact the medial rectus motoneurons of the oculomotor nucleus. Axotomy was carried out by the unilateral transection of this fascicle (right side) and produced immediate oculomotor deficits, mainly the incapacity of the right eye to adduct across the midline. Extracellular single-unit recording of abducens neurons was carried out simultaneously with eye movements. The main alteration observed in the firing of these axotomized neurons was the overall decrease in firing rate. During eye fixations, the tonic signal was reduced, and, on occasion, a progressive decay in firing rate was observed. On-directed saccades were not accompanied by the high-frequency spike burst typical of controls; instead, there was a moderate increase in firing. Similarly, during the vestibular nystagmus, neurons hardly modulated during both the slow and the fast phases. Linear regression analysis between firing rate and eye movement parameters showed a significant reduction in eye position and velocity sensitivities with respect to controls, during both spontaneous and vestibularly induced eye movements. These firing alterations were observed during the 3 month period of study after lesion, with no sign of recovery. Conversely, abducens motoneurons showed no significant alteration in their firing pattern. Therefore, axotomy produced long-lasting changes in the discharge characteristics of abducens internuclear neurons that presumably reflected the loss of afferent oculomotor signals. These alterations might be due to the absence of trophic influences derived from the target.