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Precise axon pathfinding is crucial for establishment of the initial neuronal network during development. Pioneer axons navigate without the help of preexisting axons and pave the way for follower axons that project later. Voltage-gated ion channels make up the intrinsic electrical activity of pioneer axons and regulate axon pathfinding. To elucidate which channel molecules are present in pioneer axons, immunohistochemical analysis was performed to examine 14 voltage-gated ion channels (Kv1.1–Kv1.3, Kv3.1–Kv3.4, Kv4.3, Cav1.2, Cav1.3, Cav2.2, Nav1.2, Nav1.6, and Nav1.9) in nine axonal tracts in the developing rat forebrain, including the optic nerve, corpus callosum, corticofugal fibers, thalamocortical axons, lateral olfactory tract, hippocamposeptal projection, anterior commissure, hippocampal commissure, and medial longitudinal fasciculus. We found A-type K+ channel Kv3.4 in both pioneer axons and early follower axons and L-type Ca2+ channel Cav1.2 in pioneer axons and early and late follower axons. Spatially, Kv3.4 and Cav1.2 were colocalized with markers of pioneer neurons and pioneer axons, such as deleted in colorectal cancer (DCC), in most fiber tracts examined. Temporally, Kv3.4 and Cav1.2 were expressed abundantly in most fiber tracts during axon pathfinding but were downregulated beginning in synaptogenesis. By contrast, delayed rectifier Kv channels (e.g., Kv1.1) and Nav channels (e.g., Nav1.2) were absent from these fiber tracts (except for the corpus callosum) during pathfinding of pioneer axons. These data suggest that Kv3.4 and Cav1.2, two high-voltage-activated ion channels, may act together to control Ca2+-dependent electrical activity of pioneer axons and play important roles during axon pathfinding. J. Comp. Neurol. 520:3650–3672, 2012. © 2012 Wiley Periodicals, Inc.

The pigeon vestibulocerebellum is divided into two regions based on the responses of Purkinje cells to optic flow stimuli: the uvula-nodulus responds best to self-translation, and the flocculus responds best to self-rotation. We used retrograde tracing to determine whether the flocculus and uvula-nodulus receive differential mossy fiber input from the vestibular and cerebellar nuclei. From retrograde injections into the both the flocculus and uvula-nodulus, numerous cells were found in the superior vestibular nucleus (VeS), the cerebellovestibular process (pcv), the descending vestibular nucleus (VeD), and the medial vestibular nucleus (VeM). Less labeling was found in the prepositus hypoglossi, the cerebellar nuclei, the dorsolateral vestibular nucleus, and the lateral vestibular nucleus, pars ventralis. In the VeS, the differential input to the flocculus and uvula-nodulus was distinct: cells were localized to the medial and lateral regions, respectively. The same pattern was observed in the VeD, although there was considerable overlap. In the VeM, the majority of cells labeled from the flocculus were in rostral margins on the ipsilateral side, whereas labeling from uvula-nodulus injections was distributed bilaterally throughout the VeM. Finally, from injections in the flocculus but not the uvula-nodulus, moderate labeling was observed in a paramedian area, adjacent to the medial longitudinal fasciculus. In summary, there were clear differences with respect to the projections from the vestibular nuclei to functionally distinct parts of the vestibulocerebellum. Generally speaking, the mossy fibers to the flocculus and uvula-nodulus arise from regions of the vestibular nuclei that receive input from the semicircular canals and otolith organs, respectively.

We report here the pattern of axonal branching for 11 descending cell types in the larval brainstem; eight of these cell types are individually identified neurons. Large numbers of brainstem neurons were retrogradely labeled in living larvae by injecting Texas-red dextran into caudal spinal cord. Subsequently, in each larva a single identified cell was injected in vivo with Alexa 488 dextran, using fluorescence microscopy to guide the injection pipette to the targeted cell. The filling of cells via pressure pulses revealed distinct and often extensive spinal axon collaterals for the different cell types. Previous fills of the Mauthner cell had revealed short, knob-like collaterals. In contrast, the two segmental homologs of the Mauthner cell, cells MiD2cm and MiD3cm, showed axon collaterals with extensive arbors recurring at regular intervals along nearly the full extent of spinal cord. Furthermore, the collaterals of MiD2cm crossed the midline at frequent intervals, yielding bilateral arbors that ran in the rostral-caudal direction. Other medullary reticulospinal cells, as well as cells of the nucleus of the medial longitudinal fasciculus (nMLF), also exhibited extensive spinal collaterals, although the patterns differed for each cell type. For example, nMLF cells had extensive collaterals in caudal medulla and far-rostral spinal cord, but these collaterals became sparse more caudally. Two cell types (CaD and RoL1) showed arbors projecting ventrally from a dorsally situated stem axon. Additional cell-specific features that seemed likely to be of physiological significance were observed. The rostral-caudal distribution of axon collaterals was of particular interest because of its implications for the descending control of the larva's locomotive repertoire. Because the same individual cell types can be identified from fish to fish, these anatomical observations can be directly linked to data obtained in other kinds of experiments. For example, 9 of the 11 cell types examined here have been shown to be active during escape behaviors.

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.

We studied two cartilaginous fishes and described their brainstem supraspinal projections because most nuclei in the reticular formation can be identified that way. A retrogradely transported tracer, horseradish peroxidase or Fluoro-Gold, was injected into the spinal cord of Platyrhinoidis triseriata (thornback guitarfish) or Heterodontus fransisci (horn shark). We described labeled reticular cells by their position, morpohology, somatic orientation, dendritic processes, and laterality of spinal projections. Nineteen reticular nuclei have spinal projections: reticularis (r.) dorsalis, r. ventralis pars α and β, r. gigantocellularis, r. magnocellularis, r. parvocellularis, r. paragigantocellularis lateralis and dorsalis, r. pontis caudalis pars α and β, r. pontis oralis pars medialis and lateralis, r. subcuneiformis, r. peduncularis pars compacta, r. subcoeruleus pars α, raphe obscurus, raphe pallidus, raphe magnus, and locus coeruleus. Twenty nonreticular nuclei have spinal projections: descending trigeminal, retroambiguus, solitarius, posterior octaval, descending octaval, magnocellular octaval, ruber, Edinger-Westphal, nucleus of the medial longitudinal fasciculus, interstitial nucleus of Cajal, latral mesencephalic complex, periventricularis pretectalis pars dorsalis, central pretectal, ventromedial thalamic, posterior central thalamic, posterior dorsal thalamic, the posterior tuberculum, and nuclei B, F, and J. The large number of distinct reticular nuclei with spinal projections corroborates the hypothesis that the reticular formation of elasmobranches is complexly organized into many of the same nuclei that are found in frogs, reptiles, birds, and mammals. J. Comp. Neurol. 403:534–560, 1999. © 1999 Wiley-Liss, Inc.

This study investigated whether the topographic differences in the functional properties of the tectal motor map of goldfish are related to particular patterns of connections with downstream structures. With this aim, the distribution of synaptic boutons in the mesencephalic and rhombencephalic structures was studied after discrete injections of the tracer biotinylated dextran amine were placed at separate sites along the tectal anteroposterior axis. Irrespective of the location of the injection site, the boutons were more abundant in the mesencephalon than in the rhombencephalon, and they were located chiefly ipsilaterally all throughout the brainstem. In the mesencephalon, the boutons were found in its ventrolateral reticular formation and, to a lesser extent, in the nucleus of the medial longitudinal fasciculus, the oculomotor and isthmi nuclei, and the torus semicircularis. In the mesencephalic reticular formation, the bouton location was distributed topographically with respect to the injection site. Terminals were also observed in the nucleus of the medial longitudinal fasciculus after injections into anteromedial or middle tectal zones. In the oculomotor nucleus, boutons were present exclusively in the case of the anteromedial injection. In the rhombencephalon, most boutons were found in the superior reticular formation, and their number decreased in the medial and inferior reticular formations. A topographic distribution could be observed within the superior reticular formation, although its density was attenuated compared with that observed in the mesencephalic reticular formation. The domains of synaptic endings on the ipsilateral side were different from those on the contralateral side: The ipsilateral synaptic endings were located more medially. Finally, a few boutons were also found in the vestibulocerebellar area on either the ipsilateral or the contralateral side, depending on the injection site. From these data, the authors conclude that, in goldfish, irrespective of the tectal injection site, the endings are in similar nuclei in the brainstem; however, the distribution of synaptic boutons within such nuclei can be related to the functional properties of each tectal zone.

The rostral interstitial nucleus of the medial longitudinal fasciculus (riMLF) contains excitatory and inhibitory burst neurons that are related to the control of vertical and torsional eye movements. In the present study, light microscopic examination of the immunohistochemical localization of amino acid neurotransmitters demonstrated that the riMLF in the cat contains overlapping populations of neurons that are immunoreactive to the putative inhibitory neurotransmitter gamma-aminobutyric acid (GABA) and the excitatory neurotransmitters glutamate and aspartate. By using a double-labelling paradigm, GABA-, glutamate-, and aspartate-immunoreactive neurons in the riMLF were retrogradely labelled by transport of horseradish peroxidase (HRP) from the oculomotor and trochlear nuclei. Electron microscopy showed that the oculomotor and trochlear nuclei contain synaptic endings that are immunoreactive to GABA, glutamate, or aspartate. Each neurotransmitter-specific population of synaptic endings has distinctive ultrastructural and synaptic features. Synaptic endings in the oculomotor and trochlear nuclei that are anterogradely labelled by transport of biocytin from the riMLF are immunoreactive to GABA, glutamate, or aspartate. Taken together, the findings from these complimentary retrograde and anterograde double-labelling studies provide rather conclusive evidence that GABA is the inhibitory neurotransmitter, and glutamate and aspartate are the excitatory neurotransmitters, utilized by premotor neurons in the riMLF that are related to the control of vertical saccadic eye movements.

The rostral interstitial nucleus of the medial longitudinal fasciculus (riMLF) contains premotor neurons that are related to the control of vertical and torsional saccadic eye movements. In the present study, complimentary light microscopic anterograde biocytin and retrograde horseradish peroxidase experiments have been performed to determine the organization of premotor neurons in the riMLF in the cat that are related intimately to the vertical motoneuron populations in the oculomotor and trochlear nuclei. The results indicate a rostral-caudal topographic arrangement of neurons in the riMLF that is related to the target projections to vertical downward (inferior rectus and superior oblique) and vertical upward (superior rectus and inferior oblique) motoneurons, respectively, in the oculomotor and trochlear nuclei. Both the anterograde and the retrograde studies are consistent, in that they demonstrate the tendency for downward and upward riMLF neurons to be separated spatially by a distance of approximately 0.5 mm in the rostral-caudal axis of the nucleus. The riMLF projections to inferior oblique and superior oblique motoneurons are predominantly ipsilateral. Projections to inferior rectus and superior rectus motoneurons, however, are bilateral, and, presumably, they provide one means for assuring the conjugacy of vertical saccadic eye movements. Because premotor burst neurons that encode parameters for upward or downward saccades are intermingled within the riMLF, and excitatory and inhibitory premotor neurons also coexist in this region, the findings from this study suggest that subregions of the riMLF contain coexistent populations of excitatory and inhibitory neurons that are related to opposite directions of vertical eye movements. The spatial segregation of excitatory premotor neurons in the riMLF that are related to vertical upward vs. downward movements, furthermore, provides a basis for the interpretation of vertical upward and/or downward gaze palsies that might result from discrete lesions at the mesodiencephalic junction in humans.

The morphology and soma-dendritic distribution of anterograde biocytin-labelled rostral interstitial nucleus of the medial longitudinal fasciculus (riMLF) synaptic endings in the oculomotor and trochlear nuclei have been examined by electron microscopy by using both preembedding immunoperoxidase and postembedding immunogold methods. The results indicate that three morphological types of riMLF synaptic endings are distinguishable on the basis of synaptic vesicle morphology (spheroidal, pleiomorphic, or ellipsoidal) and postsynaptic membrane specializations (asymmetrical or symmetrical). All three morphological types of riMLF synaptic endings establish synaptic connections predominantly with dendrites. Synaptic endings that contain ellipsoidal synaptic vesicles have a more proximal soma-dendritic distribution than those that contain either spheroidal or pleiomorphic synaptic vesicles. Furthermore, all three morphological types of synaptic endings are encountered in the same motoneuron subdivisions of the oculomotor and trochlear nuclei in the same experiments. The findings suggest that subregions of the riMLF contain coexistent populations of excitatory and inhibitory premotor neurons that are related to opposite directions of vertical saccadic eye movements but that project to the same motoneuron subgroups on the ipsilateral side. Both the morphology and the mode, pattern, and soma-dendritic distribution of saccade-related riMLF synaptic endings that establish synaptic connections with vertical motoneurons differ from those of excitatory and inhibitory second-order vertical vestibular synaptic endings. These differences in the synaptic organization of riMLF and second-order vestibular inputs to oculomotor and trochlear motoneurons may be related to differences in the information transferred by each source, the riMLF input conveying eye-velocity signals, and the vestibular input conveying eye-position signals.

We have studied the morphology of silver-impregnated neurons (rapid Golgi technique) in the rostral interstitial nucleus of the medial longitudinal fasciculus (riMLF), a center involved in the control of vertical and torsional saccadic eye movements. This morphological study of riMLF neurons in the rhesus monkey was undertaken to further our understanding of the functional circuitry of the oculomotor system. Our study employed Nissl, Golgi, and computer- assisted methods. The cytoarchitectonic boundaries of the riMLF and its relationships to neighboring structures were determined in both Nissl and Golgi preparations. Five (I–V) distinct morphological types of riMLF neurons were distinguished in the Golgi impregnations on the basis of soma size, dendritic size, numbers of primary dendrites, number of dendritic branch points, as well as form, number, and distribution of dendritic appendages. Type I neurons impregnated most frequently and had the most extensive and highly branched dendritic tree. Type II neurons displayed thick dendrites with complex dendritic appendages, but the dendritic tree was much more compact than that of type I cells. Type III and type V cells had fusiform somas and relatively unbranched dendritic trees but differed greatly in size as well as dendritic morphology. The type IV cell was the smallest neuron and had many characteristics of the local interneurons found in other thalamic, subthalamic, hypothalamic, and midbrain centers. The type V was the largest neuron, least frequently impregnated, and found only at rostral riMLF levels. Digitized reconstructions of each type of neuron were rotated by the computer, which revealed that the dendritic trees of types I, III, and V occupy a disk-like compartment in the riMLF neuropil. In contrast, the trees of types II and IV occupy a roughly spherical compartment. We suggest that three of the cell types are well suited for specific purposes: type II cells for receiving, topographically organized inputs that contain spatial information, type I cells for short-lead burst neuron output to the motor neurons or other premotor centers, and type IV cells for inhibitory inputs to type I cells. © 1994 Wiley-Liss, Inc.

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.

The intergeniculate leaflet (IGL), homolog of the primate pregeniculate nucleus, modulates circadian rhythms. However, its extensive anatomical connections suggest that it may regulate other systems, particularly those for visuomotor function and sleep/arousal. Here, descending IGL-efferent pathways are identified with the anterograde tracer, Phaseolus vulgaris leucoagglutinin, with projections to over 50 brain stem nuclei. Projections of the ventral lateral geniculate are similar, but more limited. Many of the nuclei with IGL afferents contribute to circuitry governing visuomotor function. These include the oculomotor, trochlear, anterior pretectal, Edinger-Westphal, and the terminal nuclei; all layers of the superior colliculus, interstitial nucleus of the medial longitudinal fasciculus, supraoculomotor periaqueductal gray, nucleus of the optic tract, the inferior olive, and raphe interpositus. Other target nuclei are known to be involved in the regulation of sleep, including the lateral dorsal and pedunculopontine tegmentum. The dorsal raphe also receives projections from the IGL and may contribute to both sleep/arousal and visuomotor function. However, the locus coeruleus and medial vestibular nucleus, which contribute to sleep and eye movement regulation and which send projections to the IGL, do not receive reciprocal projections from it. The potential involvement of the IGL with the sleep/arousal system is further buttressed by existing evidence showing IGL-efferent projections to the ventrolateral preoptic area, dorsomedial, and medial tuberal hypothalamus. In addition, the great majority of all regions receiving IGL projections also receive input from the orexin/hypocretin system, suggesting that this system contributes not only to the regulation of sleep, but to eye movement control as well.

Saccadic eye movements in the vertical plane are controlled by the rostral interstitial nucleus of the medial longitudinal fasciculus (riMLF) and the interstitial nucleus of Cajal. Eye movements in the vertical direction are accompanied by concurrent upper eye lid movements. These gaze-related lid movements are produced by the levator palpebrae superioris muscle, whose motoneurons are located in the caudal central subdivision (CCS) of the oculomotor nucleus. The neural circuits that direct such gaze-related lid movements were examined by use of both conventional and dual neuronal tracing methods in the cat. Injections of wheat germ agglutinin-conjugated horseradish peroxidase (WGA-HRP) into the area of the CCS revealed a distinctive subset of retrogradely labeled neurons located in the caudomedial portion of the riMLF. This subset of riMLF neurons was not labeled when injections were localized within the oculomotor nucleus proper, without involving the CCS. Injections of biotinylated dextran amine (BDA) that included this caudomedial riMLF region anterogradely labeled axons that projected profusely throughout the CCS. Labeled terminals were seen in close association with retrogradely labeled levator palpebrae motoneurons, which were primarily found contralateral to WGA-HRP muscle injections. Ultrastructural examination revealed that most BDA-labeled terminals contained clear spherical vesicles and formed asymmetrical synaptic contacts, primarily on the proximal dendrites of WGA-HRP-labeled motoneurons. A few had pleiomorphic vesicles. In summary, these results strongly suggest that the caudomedial part of the cat riMLF is a premotor center that monosynaptically controls lid movements in conjunction with vertical saccades.

The connections of the lateral terminal nucleus (LTN) of the accessory optic system (AOS) of the marmoset monkey were studied with anterograde 3H-amino acid light autoradiography and horseradish peroxidase retrograde labeling techniques. Results show a first and largest LTN projection to the pretectal and AOS nuclei including the ipsilateral nucleus of the optic tract, dorsal terminal nucleus, and interstitial nucleus of the superior fasciculus (posterior fibers); smaller contralateral projections are to the olivary pretectal nucleus, dorsal terminal nucleus, and LTN. A second, major bundle produces moderate-to-heavy labeling in all ipsilateral, accessory oculomotor nuclei (nucleus of posterior commissure, interstitial nucleus of Cajal, nucleus of Darkschewitsch) and nucleus of Bechterew; some of the fibers are distributed above the caudal oculomotor complex within the supraoculomotor periaqueductal gray. A third projection is ipsilateral to the pontine and mesencephalic reticular formations, nucleus reticularis tegmenti pontis and basilar pontine complex (dorsolateral nucleus only), dorsal parts of the medial terminal accessory optic nucleus, ventral tegmental area of Tsai, and rostral interstitial nucleus of the medial longitudinal fasciculus. Lastly, there are two long descending bundles: (1) one travels within the medial longitudinal fasciculus to terminate in the dorsal cap (ipsilateral >> contralateral) and medial accessory olive (ipsilateral only) of the inferior olivary complex. (2) The second soon splits, sending axons within the ipsilateral and contralateral brachium conjunctivum and is distributed to the superior and medial vestibular nuclei. The present findings are in general agreement with the documented connections of LTN with brainstem oculomotor centers in other species. In addition, there are unique connections in marmoset monkey that may have developed to serve the more complex oculomotor behavior of nonhuman primates.

The locus coeruleus is a widely projecting isthmal noradrenergic nucleus. In the zebrafish, it consists of between three and ten neurons, most of which have multiple, bilaterally projecting axons. Immunohodolgical studies show that the locus coeruleus provides most, if not all, of the noradrenergic innervation of the brain rostral to the isthmus. The pathways and targets in the zebrafish are similar to ascending coeruleal projections of other vertebrates. Axons ascend through two amin pathways: the longitudinal catecholamine bundle and the periventricular catecholamine pathway. The former is a dense meshwork of varicosity-bearing axons which ascends along the lateral longitudinal fasciculus into the mesencephalon. In the posterior tuberal area, this bundle dives ventrally and assumes a lateral position. In the diencephalon, it takes up a position ventral to the medial forebrain bundle, and follows this bundle into the telencephalon, where it joins the medial olfactory tract to enter the olfactory bulb. The periventricular catecholamine pathway is a diffuse pathway consisting of thick, smooth axons. It is associated with the medial longitudianl fasciculus. Rostral to the nucleus of the medial longitudinal fasciculus, this pathway joins the longitudinal catecholamine bundle around the medial forebrain bundle. The Periventricular pathway gives rise to coarse terminal arbors with large but sparse varicosities, whereas the longitudinal catecholamine bundle gives rise to terminal plexuses with fine and dense fibers and varicosities. Among the more densely innervated regions are the raphe nucleus, the interpeduncular nucleus, the torus semicircularis, parts of the hypothalamus, and the suprachiasmatic and preoptic areas. The tours longitudinalis, optic tectum, cerebellum, habenular complex, the dorsomedial zone of area dorsalis telencephali, and the olfactory bulb are moderately innervated. The nucleus glomerulosus, the torus lateralis and lateral subnuclei of the nucleus diffusus, and the anterior tuberal nucleus are devoid of noradrenergic innervation. © 1994 Wiley-Liss, Inc.

Medial and lateral rectus motoneurons of frogs were localized after retrograde labeling with horseradish peroxidase (HRP) injected in the medial rectus muscle or applied on the cut end of the abducens nerve. Coordinates of these cell columns were used as target areas for the injection of small amounts of HRP (20-60 nl) and [H-3]leucine (25-40 nl) and as search areas for retrogradely and anterogradely labeled internuclear neurons (INT) in in vivo and in vitro experiments. HRP injection in the medial rectus subdivision of the oculomotor nucleus (n = 6) resulted in retrograde labeling of cell bodies in the contralateral principal abducens nucleus. On the average about 16 cells per animal were found. Somatic diameters were about 13.5 +/- 2.8-mu-m (n = 32). The number and the size of these abducens internuclear neurons (AbINT) are smaller than those of lateral rectus motoneurons (n = 75;diameter: 19 +/- 3.2-mu-m). A crossed projection of AbINT to medial rectus motoneurons in the contralateral oculomotor nucleus is further supported by autoradiographic results. Following injection of [H-3]leucine into the abducens nucleus, a high density of silver grains was visible within the contralateral oculomotor nucleus, mainly in the caudal part of the oculomotor nucleus, where medial rectus motoneurons are located. Injection of [H-3]leucine in vivo (n = 4) and in vitro (n = 3) resulted in a similar high density of silver grains within the contralateral oculomotor nucleus, but the background level of silver grains was significantly higher after in vitro (264 +/- 38/2,500-mu-m2) than after in vivo injections (195 +/- 17/2,500-mu-2). HRP injection in the principal abducens nucleus (n = 9) resulted in retrograde labeling of cell bodies in the medial rectus subdivisions of the bilateral oculomotor nuclei. Ipsilateral projections predominated, with about 10 (+/- 8) labeled cells over contralateral projections (about 3 +/- 2). Average diameters of these oculomotor internuclear neurons (OcINT) were again smaller (10.8 +/- 2-mu-m;n = 18) than those of medial rectus motoneurons (14.4 +/- 3-mu-m;n = 52). In addition, retrogradely labeled cells were consistently encountered in the bilateral vestibular nuclei, the cerebellar nuclei, the dorsal brainstem caudal to the abducens nuclei, and ipsilaterally in the pretectum. Most of the vestibular neurons were located in the rostral part of the vestibular nuclear complex. These neurons might constitute part of the three-neuronal arc of the vestibulo-ocular reflex in the frog. Labeled cells in the pretectum were restricted to the ipsilateral posterior thalamic nucleus (P). After abducens injections the number of retrogradely labeled neurons in the P differed on the average by a factor of ten, depending on the micropipette's direction to the injection site. A ventral approach through the medial longitudinal fasciculus (MLF) resulted (as in other studies) in a false-positive overestimation of the number of P neurons projecting to the abducens nucleus, probably due to labeling of fibers of passage in the MLF. Many axons of these P neurons descend more caudally and project to an area where retrogradely labeled neurons are found after oculomotor or abducens HRP injections. Location and input-output relations of these neurons are compatible with a prepositus hypoglossi nucleus in frogs.

Motoneurons of the spinal nucleus of the bulbocavernosus (SNB) occupy a distinct dorsomedial position in the ventral horn of lumbar segments 5 and 6 and innervate sexually dimorphic striated muscles of the rat perineum, including the bulbocavernosus and levator ani. To begin the study of brain influences upon SNB function, we used retrograde tracers to identify brain regions that project to the area of SNB motoneurons. Our findings provide strong evidence that lateral vestibular and several reticular nuclei innervate the SNB. Additional possible afferents include the superior and medial vestibular nuclei, raphe nucleus, red nucleus, interstitial nucleus of the medial longitudinal fasciculus, and paraventricular nucleus.

The efferent and afferent pathways of the chick tangential nucleus were studied by using horseradish peroxidase (HRP: Sigma type VI) to label nerve cell bodies and fibers. Depositions of HRP into the tangential nucleus, as well as into the second cervical level of the spinal cord, show that the axons of tangential neurons on leaving the nucleus form an anteriorly coursing tract that passes through the ventrolateral vestibular nucleus without branching and then to the contralateral medial longitudinal fasciculus (MLF). Within the MLF, the tangential axons course posteriorly, forming collaterals that innervate the abducens nucleus, and then proceed to the cervical spinal cord. This pathway was demonstrated for the axons of the two main neurons, the principal and elongate cells, in 1-day, 1-week, and 7-week-old animals. In addition, we propose the existence of an unidentified, ipsilateral pathway to the spinal cord for the tangential axons, since HRP injections into one side of the spinal cord resulted in the bilateral labeling of tangential neurons. No labeled cells were found in the tangential nucleus following HRP depositions into the uvula, flocculus, pontine reticular formation, nucleus piriformis, nucleus jumeaux, vestibulocerebellar nucleus, retrotangential nucleus, or the dorsomedial part of the medial vestibular nucleus. The tangential nucleus receives afferents from the colossal vestibular fibers (spoon endings), small collaterals of fine vestibular ampullary fibers, flocculus, and high cervical levels of the spinal cord. From our small sample, it appears that the spinal cord fibers form most of the afferent terminals in the tangential nucleus in 1-day, 1-week, and 7-week-old animals.

Abducens motoneurons and internuclear neurons were identified electrophysiologically in anesthesized, paralyzed cats and stained by intracellular injection of horseradish peroxidase. Neurons were reconstructed and surface area of selected cells measured by light microscopy. Surface area of motoneurons and internuclear neuron with similar soma size and shape were roughly comparable. Dendrites of motoneurons were highly tapered and highly branched. By contrast, dendrites of internuclear neurons were less tapered and less branched. Axons of motoneurons had no collaterals within the brainstem. Internuclear axons crossed the midline at the level of their parent somata and ascended in the medial longitudinal fasciculus toward the oculomotor nucleus. Approximately 30% of the internuclear axons branched in the contralateral medial longitudinal fasciculus sending a fine collateral caudal toward the prepositus hypoglossi nucleus. The results suggest that, on the average, structural correlates of injected neurons (i.e., soma-dendritic morphology) can account at least in part for the earlier firing and higher intraburst frequencies of internuclear neurons versus motoneurons during on-direction rapid eye movements in alert cats.

The motor nuclei of the oculomotor, trochlear, and abducens nerves of the reptile Varanus exanthematicus and the neurons that subserve the sensory innervation of the extraocular muscles were identified and localized by retrograde and anterograde transport of horseradish peroxidase (HRP). The highly differentiated oculomotor nuclear complex, located dorsomedially in the tegmentum of the midbrain, consists of the accessory oculomotor nucleus and the dorsomedial, dorsolateral, intermediate, and ventral subnuclei. The accessory oculomotor nucleus projects ipsilaterally to the ciliary ganglion. The dorsomedial, dorsolateral, and intermediate subnuclei distribute their axons to the ipsilateral orbit, whereas the ventral subnucleus, which innervates the superior rectus muscle, has a bilateral, though predominantly contralateral projection. The trochlear nucleus, which rostrally overlaps the oculomotor nuclear complex, is for the greater part a comma-shaped cell group situated lateral, dorsal, and medial to the medial longitudinal fasciculus. Following HRP application to the trochlear nerve, almost all retrogradely labeled cells were found in the contralateral nucleus. The nuclear complex of the abducens nerve consists of the principal and accessory abducens nuclei, both of which project ipsilaterally. The principal abducens nucleus is located just beneath the fourth ventricle laterally adjacent to the medial longitudinal fasciculus and innervates the posterior rectus muscle. The accessory abducens nucleus has a ventrolateral position in the brainstem in close approximation to the ophthalmic fibers of the descending trigeminal tract. It innervates the retractor bulbi and bursalis muscles. The fibers arising in the accessory abducens muscles form a loop in or just beneath the principal abducens nucleus before they join the abducens nerve root. The afferent fibers conveying sensory information from the extraocular muscles course in the oculomotor nerve and have their perikarya in the ipsilateral trigeminal ganglion, almost exclusively in its ophthalmic portion.

The origins of the descending spinal pathways in sea lampreys (Petromyzon marinus), silver lampreys (Ichthyomyzon unicuspis), and Pacific hagfish (Eptatretus stouti) were identified by the retrograde transport of horseradish peroxidase (HRP) placed in the rostral spinal cord. In lampreys, the majority of HRP-labeled cells were located along the length of the brainstem reticular formation in the inferior, middle, and superior reticular nuclei of the medulla, mesencephalic tegmentum, and nucleus of the medial longitudinal fasciculus. Labeled reticular cells included the Mauthner and Müller cells. Horseradish-peroxidase-filled cells were also present in the descending trigeminal tract, intermediate and posterior octavomotor nuclei, and a diencephalic cell group, the nucleus of the posterior tubercle. As in lampreys, the reticular formation of the Pacific hagfish was the largest source of descending afferents to the spinal cord. Labeled cells were found in the dorsolateral and ventromedial reticular nuclei, the dorsal tegmentum at the juncture of the medulla and midbrain, and the nucleus of the medial longitudinal fasciculus. Additional medullary cells projecting to the cord were located in the perivagal nucleus, the central gray, and the anterior and posterior magnocellular octavolateralis nuclei. The existence of reticulospinal and possible vestibulo-, trigemino-, and solitary spinal projections in lampreys and hagfishes and the wide distribution of these pathways in jawed vertebrates suggest that they evolved in the common ancestor of gnathostomes and both groups of jawless fishes. However, descending spinal pathways from the cerebellum, red nucleus, and telencephalon appear to be gnathostome characters.

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 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 fee 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.

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.

In order to study brainstem origins of spinal projections, ten Tegu lizards (Tupinambis nigropunctatus) received complete or partial hemisections of the spinal cord at the first or second cervical segment. Their brains were processed for conventional Nissl staining. The sections were surveyed for the presence or absence of retrograde chromatolysis. Based on analysis and comparison of results from lesions in the various spinal cord funiculi, the following conclusions were reached: The interstitial nucleus projects ipsilaterally to the spinal cord via the medial longitudinal fasciculus, as does the middle reticular field of the metencephalon. The red nucleus and dorsal vagal motor nucleus both project contralaterally to the spinal cord via the dorsal part of the lateral funiculus. The superior reticular field in the rostral metencephalon and the ventrolateral vestibular nucleus project ipsilaterally to the spinal cord via the ventral funiculus. The dorsolateral metencephalic nucleus and the ventral part of the inferior reticular nucleus of the myelencephalon both project ipsilaterally to the spinal cord via the dorsal part of the lateral funiculus. Several brainstem nuclei in Tupinambis project bilaterally to the spinal cord. The ventrolateral metencephalic nucleus, for example, projects ipsilaterally to the cord via the medial longitudinal fasciculus and contralaterally via the dorsal part of the lateral funiculus. The dorsal part of the inferior reticular nucleus projects bilaterally to the spinal cord via the dorsal part of the lateral funiculus. The nucleus solitarius complex projects contralaterally via the dorsal part of the lateral funiculus but ipsilaterally via the middle of the lateral funiculus. The inferior raphe nucleus projects bilaterally to the spinal cord via the middle part of the lateral funiculus. These data suggest that supraspinal projections in reptiles, especially reticulospinal systems, are more highly differentiated than previously thought. On the other hand, recent findings in cat, opossum, and monkey reveal that the organization of supraspinal pathways in the Tegu lizard bears a striking resemblance to that observed in mammals.

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 wert 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 drosally 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. The oculomotor system of the goldfish is similar to that found in other teleosts and higher vertebrates, displaying characteristics of an animal whose eye movements cover all regions of its external environment.

The projections of the medial terminal nucleus (MTN) of the accessory optic system have been studied in the rabbit and rat following injection of 3H-leucine or 3H-leucine/3H-proline into the MTN and the charting of the course and terminal distribution of the MTN efferents. The projections of the MTN, as demonstrated autoradiographically, have been confirmed in retrograde transport studies in which horseradish peroxidase (HRP) has been injected into nuclei shown in the autoradiographic series to contain fields of terminal axons. The following projections of the MTN have been identified in the rabbit and rat. The largest projection is to the ipsilateral nucleus of the optic tract and dorsal terminal nucleus (DTN) of the accessory optic system. Labeled axons course through the midbrain reticular formation and the superior fasiculus, posterior fibers of the accesssory optic system, to reach the nucleus of the optic tract and the DTN in both rabbit and rat. Axons also run forward to traverse the lateral thalamus and to distribute to rostral portions of the nucleus of the optic tract in rat only. A second, large projection is to the contralateral dorsolateral portion of the nucleus parabrachialis pigmentosus of the ventral tegmental area together with an adjacent segment of the midbrain reticular formation. The patchy terminal field observed has been named the visual tegmental relay zone (VTRZ). This fiber projection courses within the posterior commissure and along its path to the VTRZ, provides terminals to the interstitial nucleus of Cajal and the nucleus of Darkschewitsch, both bilaterally. A third, large MTN projection distributes ipsilaterally to the deep mesencephalic nucleus, pars medialis, and the oral pontine reticular formation. Further, this projection also supplies input to the medial nucleus of the periaqueductal gray matter, bilaterally in the rabbit and rat, and in the rabbit also to the ipsilateral superior and lateral vestibular nuclei. A fourth projection crosses the midline and courses caudally to reach, contralaterally, the dorsolateral division of the basilar pontine complex and the above nuclei of the vestibular complex. A fifth projection of the MTN utilizes the medial longitudinal fasciiculus to reach the rostral medulla, in which its axons distribute ispilaterally to the dorsal cap, its ventrolateral outgrowth, and the beta nucleus of the inferior olivary complex. There is also a contralateral contingent of this projection that leaves the medial longitudinal fasciculus to innervate a small rostral segment of the contralateral dorsal cap. The findings from the autoradiographic series further reveal that the MTN and/or protions of the ventral tegmental area or substantia nigra that lie adjacent to the MTN and that are included in the tritiated amino acid injections provide inputs ipsilaterally to (1) the interstitial nuclei of the superior fasciculus, posterior fibers and the lateral terminal nuclei of the accessory optic system; (2) the dorsolateral and medial divisions of the basilar pontine complex; (3) the ventral nucleus of the lateral leminiscus; (4) the infratrigeminal nucleus; (5) the nucleus subcoerulus; (6) the pontine periventricular gray; and (7) the ventral division of the parabrachial nucleus.

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.

The projection regions of electroreceptor and mechanical lateral line afferents in electric fish of the mormyridae family are described. Electroreceptor afferents from the posterior dorsal skin run in the dorsal branch of the posterior lateral line nerve. Electroreceptor afferents from ventral skin and mechanical lateral line afferents and efferents run in the ventral branch of the nerve. Horseradish peroxidase (HRP) injections into each branch resulted in filling of its central terminals with the marker enzyme. The method yields a Golgi-like staining of afferent terminals, allowing some aspects of their morphology to be described. Comparison of results from dorsal and ventral branch injections shows the separate medullary regions to which electroreceptor and mechanical afferents project, and also demonstrates four separate somatotopic maps within the electroreceptor region. Mechanical afferents end predominantly ipsilaterally in nucleus anterior and eminentia granularis as has been suggested by others. Ipsilateral endings in nucleus octavius are also seen. Electroreceptor afferents end exclusively in the cortex and nucleus of posterior lateral line lobe (PLLL). Within the cortex there are three distinct maps of the skin surface which are separated from each other by discontinuities in the cellular layers. Somatotopic mapping is also present in the nucleus of PLLL though it is less precise than in the cortical zones. Large club endings of the cells of this nucleus are filled with HRP. Labeled cells are seen within a small midline nucleus located at the level of the eighth nerve just above the medial longitudinal fasciculus. These are probably the cell bodies of lateral line efferents.

The medial accessory nucleus of Bechterew, a vertically oriented cell group in the rostral lateral oculomotor nucleus (OMN), contiguous dorsally with the nucleus of Darkschewitsch (ND) and ventrally with the parvocellular red nucleus, is separated from the interstitial nucleus of Cajal (IC) by a small paraoculomotor fascicle (POF) that forms the anatomical limits of the OMN. Horseradish peroxidase (HRP) gel implants in the prearcuate frontal cortex dorsal to the caudal third of the principal sulcus in the monkey resulted in an anterogradely labeled bilateral projection to this paraoculomotor cell group. The functional role of this largely overlooked nucleus is yet to be determined. However, the failure to retrogradely label following HRP injections involving both the extraocular muscles and ciliary ganglion suggests that it cannot be classified as belonging to either the somatic or the visceral cell column at the present time. We suggest that, like IC and ND, it probably contributes to the POF of the medial longitudinal fasciculus and may be involved in internuclear connections. There is little doubt that it has been involved inadvertently in studies of oculomotor connections.

Pause neurons (PNs) are inhibitory neurons close to the midline at the pontomedullary junction that fire tonically and then cease firing just prior to quick eye movements of visual or vestibular origin. Previous physiological evidence has shown that these neurons have a role of central importance in the generation of rapid eye movements in any direction and all major models of ocular motor control incorporate PNs as major elements. In this study in cats, we injected horseradish peroxidase intracellularly into somata or axons of physiologically identified PNs. After appropriate tissue preparation, cell body and axonal reconstructions were performed, with the aid of a camera lucida-equipped microscope. Fifty-three PNs were stained and reconstructed. These consisted of 17 cell bodies and dendrites and 36 axons. Seven of these included both cell bodies and axons. PN somas lay close to the midline in the nucleus raphe pontis and centralis superior, had extensive dendritic arborizations tending to arise from either pole of the elongated soma, and had axons which typically crossed the midline and bifurcated into long branches which extended rostrally and caudally, inferior to the medial longitudinal fasciculus. There were major terminal arborizations and boutons in areas just rostral and caudal to the abducens nucleus in areas where two types of premotor neurons, excitatory and inhibitory burst neurons, are concentrated. Many axosomatic contacts were noted. Other terminal arborizations and boutons were found close to the midline in a region rostral to abducens nucleus containing other neurons known to burst prior to quick eye movements, and in the nucleus reticularis gigantocellularis. Rostral stem axons could be traced to the level of the trochlear nucleus and inferior to the medial longitudinal fasciculus. The caudal stem axons could be traced parallel to the midline and inferior to the medial longitudinal fasciculus and as far caudally as the hypoglossal nucleus.

In 16 monkeys attempts were made to produce localized unilateral and bilateral lesions in the medial longitudinal fasciculus (MLF) in the pons in order to study resulting disturbances of eye movements and fiber degeneration. Noteworthy physiological findings could be correlated with lesions and fiber degeneration in eight animals. Degeneration was studied by the Nauta technic. Bilateral lesions of the MLF between the abducens nuclei impair all horizontal eye movements, except convergence. Unilateral lesions of the MLF rostral to the abducens nuclei produce: (1) paresis of ipsilateral ocular adduction on attempted lateral gaze and (2) monocular horizontal nystagmus in the contralateral abducting eye. Bilateral lesions in the latter location produce these disturbances bilaterally. Paresis of ocular adduction resulting from lesions in the MLF is associated with ascending degeneration in the MLF projecting differentially upon cells of the ventral nucleus of the oculomotor complex, a cell group innervating the ipsilateral medial rectus muscle. Monocular horizontal nystagmus in the contralateral abducting eye appears to be a consequence of interruption of either: (1) descending fibers in the MLF, or (2) secondary vestibular fibers passing to the opposite abducens nucleus. Unilateral lesions of the MLF rostral to the abducens nucleus produce degeneration ipsilaterally in: (1) the nuclei of the extraocular muscles, (2) the interstitial nucleus (Cajal), and (3) parts of the ventral posterior inferior, ventral posterior medial, parafascicular, centromedian, and recticular nuclei of the thalamus.

The innervation of extraocular muscles in the rabbit was studied by using the methods of horseradish peroxidase (HRP) histochemistry, gross dissection, and quantitative morphology. Subdivisions of the oculomotor complex that innervate the superior rectus, inferior rectus, medial rectus, and inferior oblique and levator palpebrae are described, and our results are in agreement with previous accounts of the projections of this nucleus. Our analysis of the innervation of the lateral rectus and retractor bulbi muscles, however, differs from previous descriptions. The axons of approximately 80% of neurons in the abducens nucleus are in the VIth nerve and innervate the lateral rectus muscle, and approximately 15-20% are internuclear neurons both surrounding and intermingling with the motor neurons of the abducens nucleus. The interneurons project to the medial rectus subdivision of the contralateral oculomotor complex via the medial longitudinal fasciculus (MLF). Neurons in both the abducens and the accessory abducens nucleus innervate the retractor bulbi muscles via the VIth nerve. All neurons in the accessory abducens nucleus innervate the retractor bulbi muscles, but gross dissection revealed that the retractor bulbi is also innervated by the IIIrd nerve. The bases for differences between our data and previously published descriptions are discussed. The trochlear nucleus of the rabbit has not been previously studied by methods of axonal transport. The body of the nucleus, its caudal tail, the trajectories of axons entering the trochlear nerve, and soma size distributions are described. The trochlear nucleus contains approximately 900 neurons; most are motoneurons the axons of which travel in the trochlear nerve and decussate in the anterior medullary velum. Approximately 3% of trochlear motor neurons innervate the ipsilateral superior oblique muscle. Their soma size is significantly smaller than that of contralaterally projecting neurons. For comparative purposes, the innervation of extraocular muscles by the trochlear nerve was also investigated in several rodents and carnivores. In all animals studied, the percentage of trochlear neurons innervating the ipsilateral superior oblique muscle was strikingly uniform (2-4%). Gross dissection of the extraocular muscles revealed in the rabbit a muscle, innervated by the trochlear nerve, for which we propose the name "tensor trochleae." In the rabbit, this muscle is innervated by approximately one-third of the trochlear motor neurons.(ABSTRACT TRUNCATED AT 400 WORDS)

This study utilizes retrograde axonal transport of cobaltous-lysine, and conventional silver and Golgi staining techniques to study the abducens motor nucleus innervating the external rectus muscle of the carpet shark. The nucleus consists of 300-400 motoneurons located immediately ventrolateral to the medial longitudinal fasciculus (MLF), distributed over about 1.25 mm in a rostrocaudal direction at the level of exit of the VI nerve. The axons of the motoneurons form seven or eight discrete ventrally directed fascicles which, having exited from the brainstem, group together to form the abducens (VI) nerve. The motoneurons are on average about 16 micron in diameter, are bipolar, and their dendrites have a transverse orientation. Typically one set of dendrites penetrates the MLF and the other set extends ventrally into the reticular formation.

The autoradiographic tracing method has been used to analyze the distribution of ascending tectofugal pathways in the rhesus monkey. Our findings show that axons which arise from deep collicular neurons terminate within several dorsal thalamic nuclei which in turn project upon the frontal eye fields (area 8) and the inferior parietal lobule (area 7). Both of these cortical areas are functionally quite similar to the deep colliculus, and we suggest that ascending channels from the deep tectum must account, at least in part, for these functional similarities. The present autoradiographs reveal projections to several nuclear zones previously not identified as deep collicular targets in the monkey. Such targets include the visceral cell columns of the oculomotor complex, the rostral interstitial nucleus of the medial longitudinal fasciculus, and the magnocellular division of the ventral anterior nucleus. Deep tectal input also has been shown to terminate quite extensively within the paralamellar region of the mediodorsal nucleus and in the parafascicular nucleus; very little input to the central lateral and centromedian nuclei was observed. Radioisotope injections restricted to the superficial layers reveal dense projections to the parabigeminal nucleus, the pretectum, the inferior and lateral pulvinar nuclei, and to the ventral and dorsal lateral geniculate nuclei. Transported protein within the dorsal lateral geniculate nucleus occupied the "S" layers and the interlaminar zones.

There are three different descending projections from the bulbar gigantocellular tegmental field (BFTG) in the cat, as defined by intracellular recording and intracellular horseradish peroxidase (HRP) techniques. The first pathway arises from neurons which send axons to the contralateral medial longitudinal fasciculus (cMLF neurons); cMLF neurons show excitatory postsynaptic potentials (EPSPs) after stimulation of the ipsilateral pontine gigantocellular tegmental field (PFTG). Most cMLF neurons have large ellipsoid-polygonal somata (mean, 56.8 micron), thick axons (average diameter, 3.09 microns), mostly non-spiny dendrites and dendritic fields flattened in the anteroposterior direction. No cMLF neurons with axon collaterals in the BFTG are present in the data of this study. The second pathway arises from neurons which send axons to the ipsilateral MLF (iMLF neurons); iMLF neurons show EPSPs after stimulation of the ipsilateral PFTG. Most iMLF neurons have large ellipsoid-polygonal somata (mean, 60.2 microns), thick axons (average diameter, 3.00 microns), mostly non-spiny dendrites and dendritic fields that are only slightly flattened in the anteroposterior direction. As with cMLF neurons, no iMLF neurons with axon collaterals in the BFTG are present in the data of this study. The third pathway arises from neurons that send axons directly into the ipsilateral caudal bulbar reticular formation (iBRF neurons). Most iBRF neurons have smaller ellipsoid-polygonal somata (mean, 38.6 microns), thinner axons (average diameter, 1.84 microns), mostly nonspiny dendrites, and dendritic fields that are flattened in the anteroposterior direction. In contrast to cMLF and iMLF neurons, axon collaterals are present in 73% of iBRF neurons. About half of iBRF neurons have bifurcated axon collaterals with both anterior and posterior projections, and in these neurons antidromic spike potentials are elicited by stimulation of the ipsilateral PFTG.

The localization of the motor neurons innervating the extraocular muscles in the oculomotor nuclei of adult cats and rabbits was investigated by means of retrograde labelling with horseradish peroxidase (HRP). The groups consisting of the motor neurons innervating an individual muscle lay in the nucleus as elongated columns extending in a longitudinal direction. The position of each group in the transverse section varied according to the rostro-caudal level of the nucleus. In the cat and rabbit, entire contralateral innervation of the superior rectus and entire ipsilateral innervation of three muscles of the inferior rectus, medial rectus and inferior oblique were similarly observed. However, the arrangement of individual motor groups differed considerably in both animals except for the group innervating the inferior rectus which was generally found in the ventral position running through the rostral two-thirds of the oculomotor nucleus. In the case of cats, the central caudal nucleus bilaterally innervated the levator palpebrae superioris. The motor neurons innervating this muscle in the rabbit (which lacks the central caudal nucleus) formed a rostro-caudal club-shaped column close to the group innervating the superior rectus. The aberrant cellular mass in the adjoining medial longitudinal fasciculus which belongs to the medial rectus appears to play an important role in the eye movement, because it commonly appears in various animals.

The afferent and efferent connections of the nucleus prepositus hypoglossi with brainstem nuclei were studied using anterograde and retrograde axonal transport techniques, and by intracellular recordings and injections of horseradish peroxidase into prepositus hypoglossi neurons. The results of experiments in which horseradish peroxidase was injected into the prepositus hypoglossi suggest that the major inputs to the prepositus hypoglossi arise from the ipsi- and contralateral perihypoglossal nuclei (particularly the prepositus hypoglossi and intercalatus), vestibular nuclei (particularly the medial, inferior, and ventrolateral nuclei), the paramedian medullary and pontine reticular formation, and from the cerebellar cortex (flocculus, paraflocculus, and crus I; the nodulus was not available for study). Regions containing fewer labeled cells included the interstitial n. of Cajal, the rostral interstitial n. of the medial longitudinal fasciculus, the n. of the posterior commissure, the superior colliculus, the n. of the optic tract, the extraocular motor nuclei, the spinal trigeminal n., and the central cervical n. The efferent connections of the prepositus hypoglossi were studied by injecting 3H-leucine into the prepositus hypoglossi, and by following the axons of intracellularly injected prepositus hypoglossi neurons. The results suggest that in addition to the cerebellar cortex, the most important extrinsic targets of prepositus hypoglossi efferents are the vestibular nuclei (particularly the medial, inferior, and ventrolateral nuclei, and the area X), the inferior olive (contralateral dorsal cap of Kooy and ipsilateral subnucleus b of the medial accessory olive), the paramedian medullary and pontine reticular formation, the reticular formation surrounding the parabigeminal n., the contralateral superior colliculus and pretectum, the extraocular motor nuclei (particularly the contralateral abducens nucleus and the ipsilateral medial rectus subdivision of the oculomotor nucleus), the ventral lateral geniculate n., and the central lateral thalamic nucleus. Other areas which were lightly labeled in the autoradiographic experiments were the contralateral spinal trigeminal n., the n. raphe pontis, the Edinger Westphal n., the zona incerta, and the paracentral thalamic n. Many of the efferent connections of the prepositus hypoglossi appear to arise from principal prepositus hypoglossi neurons whose axons collateralize extensively in the brainstem. On the other hand, small prepositus hypoglossi neurons project to the inferior olive, and multidendritic neurons project to the cerebellar flocculus, apparently without collateralizing in the brainstem.(ABSTRACT TRUNCATED AT 400 WORDS)

Tectoreticular projections in turtles were examined by reconstructing from serial sections axons that were anterogradely filled with horseradish peroxidase after tectal injections. Three tectoreticular pathways each contain extensively collateralized axons. The crossed dorsal pathway (TBd) contains large and small caliber axons. After leaving the tectum, TBd axons emit collaterals into the ipsilateral profundus mesencephali rostralis and then give off a main rostral branch that bears secondary collaterals in the ipsilateral interstitial nucleus of the medial longitudinal fasciculus and the suprapeduncular nucleus. The main trunks cross the midline and descend in the predorsal bundle, generating collaterals at regular intervals. These terminate mostly in the medial half of the reticular core from the midbrain to the caudal medulla. Axons in the uncrossed intermediate pathway also emit collaterals into a midbrain reticular nucleus (profundus mesencephali caudalis) and often have a thick rostral branch. The main caudal trunks, however, remain ipsilateral and travel in a diffuse, laterally placed tract, where each emits a long series of collaterals into the lateral half of the reticular core. The uncrossed ventral pathway (TBv) contains medium and small caliber axons. TBv axons often have collaterals within the tectum and apparently lack main rostral branches. Their caudal trunks run in the tegmental neuropile below the TBi where they collateralize less exuberantly than do TBd and TBi axons. The morphology of axons in all three pathways suggests that projections from disjunct tectal loci converge at many rostrocaudal levels within the reticular formation. This point was examined explicitly in experiments in which two disjunct injections were placed in one tectal lobe. Intermediate pathway axons traced from the two loci initially formed two distinct bundles but then intermingled in the reticular formation.

Horseradish peroxidase (HRP) was used to determine the sequence in which axons from different brain neurons reach the tail spinal cord during embryonic and early larval development of Xenopus laevis. Brainstem cells of several classes project to the tail at these stages: mesencephalic reticulospinal neurons of the nucleus of the medial longitudinal fasciculus, a variety of other reticulospinal neurons, vestibulospinal neurons, and a group of median basal cells which may be raphe neurons. Among the reticulospinal neurons the paired Mauthner cells are the most prominent. They and caudally situated reticular neurons are the first to label with HRP applied to the tail spinal cord (stage 37). Vestibulospinal and other reticular neurons begin to label next (stage 39), followed by mesencephalic and then median basal neurons (stage 41). Except for the Mauthner cells, the number of labeled cells belonging to each neuron class increases gradually as development proceeds.

The projections of the medial part of the deep mesencephalic nucleus (DMN) were traced by autoradiography and retrograde horseradish peroxidase (HRP) techniques. No ascending projections were observed from the medial part of the DMN; however, two groups of descending fibers were observed. One group crossed the midline and coursed to the caudal part of the red nucleus. At this point, these fibers divided into two distinct bundles. One bundle of fibers passed caudally to terminate in the contralateral pontine reticular nucleus, superior olive-trapezoid body complex, gigantocellular nucleus, and upper cervical spinal cord. The other bundle entered the medial longitudinal fasciculus (MLF) and coursed through the pons and medulla without termination, to enter the cervical spinal cord where terminations were noted in the dorsal horn. The other group of fibers from the medial DMN descended through the ipsilateral pons and medulla, projecting to the pontine reticular nucleus, superior olive-trapezoid body complex, gigantocellular nucleus, and upper cervical spinal cord. These findings indicate that the medial part of the DMN is likely to be involved in complex sensorimotor events via reticulobulbar and reticulospinal connections.

The origins of descending spinal projections in the lepidosirenid lungfishes were identified by retrograde transport of horseradish peroxidase (HRP) introduced into the rostral spinal cords of juvenile African (Protopterus annectans and Protopterus amphibians) and South American (Lepidosiren paradoxa) lungfishes. Standard HRP histochemistry revealed retrogradely labeled neurons in the nucleus of the medial longitudinal fasciculus, midbrain tegmentum, red nucleus, optic tectum, mesencephalic trigeminal nucleus, granule cell layer of the cerebellum, superior, middle, and inferior medullary reticular nuclei, magnocellular and descending octaval nuclei, region of the descending trigeminal tract, solitary complex, and the margins of the spinal gray matter anterior to the spinal HRP implant. A small number of retrogradely labeled neurons were also present in the ventral thalamus of Protopterus. A descending spinal projection from the forebrain was not evident in either genus of lepidosirenid lungfishes. The presence of projections to the spinal cord from the diencephalon, medial reticular formation of the midbrain and medulla, octaval (vestibular) nuclei, solitary complex, and probable nucleus of the descendin trigeminal tract in lungfishes and their overall similarity to comparable projections in other vertebrates suggest that these pathways are among those representative of the primitive pattern of descending spinal projections in vertebrates.

The accessory optic system of Rana pipiens was investigated by autoradiographic, horseradish peroxidase, and Golgi techniques, revealing a complexity of neuroanatomical organization previously unrecognized. Retinal afferents project to the nucleus of the basal optic root (nBOR) via a primary bundle and more diffuse, medial bundle of optic axons, both of which contain large- and small-diameter fibers. At least six types of retinal ganglion cell contribute to the basal optic root (BOR), including giant ganglion cells, two intermediate-sized ganglion cell types, small ganglion cells, and two types of displaced ganglion cell. The major retinal projection is contralateral, but a small, ipsilateral component also exists. Afferents from neurons which are postsynaptic to the thalamic retinal terminal fields also reach nBOR. Four distinct cell types were identified within the terminal field of nBOR: stellate neurons (63%), amacrine cells (19%), elongate neurons (14%), and large ganglionic neurons (4%). Both stellate and amacrine cells appear to be intrinsic neurons, while elongate and ganglionic neurons constitute the efferent neuron population of nBOR. In addition, cells which lie medial to the terminal field, pyriform and commissural neurons, send dendrites into nBOR. Pyriform neurons project to the nucleus of the medial longitudinal fasciculus (nMLF) and cranial nerve nuclei III and IV, while commissural neurons project to the contralateral nBOR. Large reticular neurons of the nMLF also send dendrites into nBOR. Efferent projections from nBOR were observed in the large-celled pretectal nucleus and in nucleus lateralis profundus. A second major projection originates from the peri-nBOR region and is associated with the oculomotor system and with the nMLF. Efferent projections from the nMLF to the vestibular nuclei and to the rostral spinal cord were also observed, as well as projections which reach the brainstem from the large-celled pretectal nucleus, the posterior thalamic and anterior mesencephalic central gray.

The first expression and distribution of acetylcholinesterase (AChE) activity was studied among a distinct population of early neurons in embryonic zebrafish by using histochemical and retrograde labeling techniques. AChE first appeared in the nervous system in the primary motoneurons of the rostral spinal cord when the embryo had nine somites, approximately 14 hours postfertilization. Subsequent expression of AChE activity in the spinal cord proceeded in a rostral-to-caudal sequence. Cranial neurons expressed AChE activity shortly after it appeared in the rostral spinal cord. Several hours later, near the end of the first day, primary neurons in the hind-brain and spinal cord all contained AChE, including sensory neurons, reticulospinal interneurons, and primary motoneurons. AChE activity was also detected in the nucleus of the medial longitudinal fasciculus. Presumptive cranial ganglia transiently expressed AChE activity between 14 and 24 hours of development. These results, combined with previous observations that examined the time of origin and axogenesis of primary neurons, suggest that primary neurons in the embryonic zebrafish contain AChE before they sprout axons. The primary neurons appear to follow a common sequence of development consisting of a withdrawal from the cell division cycle, the expression of AChE, and axogenesis. Although this sequence is followed by all primary neurons, lack of a rostral-to-caudal sequence in the time of birth and variability in the time of axon outgrowth demonstrate that the relative timing of these three events is not rigidly programmed in individual neurons. Moreover, the very early expression of AChE in such diverse cell types suggests that it may have a developmental role in addition to its function in transmitter metabolism.

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.

Cortical projections to cell groups surrounding the oculomotor complex were studied by using the retrograde and anterograde capabilities of the horseradish peroxidase (HRP) technique in old and new world monkeys. Fluid HRP injections or transcannular solid polyacrylamide HRP gel implants were made into the oculomotor nucleus (OMN) and adjacent nuclei to label retrogradely corticofugal neurons that project to this region, and cortical HRP gel implants were made in various areas of the frontal lobe to label anterogradely the trajectories and terminations of cortico-paraoculomotor projections and thus to confirm the retrograde findings. Projections to the paraoculomotor cell groups in the medial dien-mesencephalic tegmentum originate almost exclusively from the frontal lobe. Both retrograde and anterograde studies confirmed that the prearcuate cortex in the concavity of the arcuate sulcus, including the frontal eye field, and, to a lesser extent, suprarcuate rostral dorsal area 6 cortex and the dorsomedial convexity (area 9), project to the rostral interstitial nucleus of the medial longitudinal fasciculus (riMLF) in the dorsal region of the prerubral field, nucleus of Darkschewitsch (ND), medial accessory nucleus of Bechterew (NB) and dorsomedial parvocellular red nucleus (dmPRN). The premotor area 6 and motor area 4 cortex, on the other hand, give rise to projections that target a larger portion of the parvocellular red nucleus, extending rostrally into the ventral region of the prerubral field, and a rather intense projection to the ND. The interstitial nucleus of Cajal (IC) was distinguished more by its light, or lack of, projections from the frontal cortex. The inferior parietal lobule (IPL, area 7) which has certain common physiological properties with the frontal eye field (FEF area 8) related to the oculomotor system, lacked retrogradely labeled neurons in all cases where transcannular gel implants into the OMN eliminated the possibility of HRP uptake in the corpus callosum or other structures traversed in needle injections, suggesting that the IPL affects eye movement primarily through its rostrally directed corticocortical associational connections with the FEF. In additional cases, the ND-NB-dmPRN configuration of cells that receives FEF input is shown to project to the inferior olivary complex (i.e., is pre-olivo-cerebellar), whereas riMLF and IC give rise to descending projections in the MLF, which target extraocular muscle motor nuclei, vestibular complex, and spinal cord. The results are discussed in terms of the potential role of the cerebral cortex in eye movement mechanisms.

The trajectories and the cells of origin of the pontobulbar gigantocellular tegmental field descending pathways were studied in the cat using anterograde WGA-HRP and retrograde HRP techniques. Four main descending pathways and cells of origin were delineated: (1) Predominantly large neurons in the pontine gigantocellular tegmental field (average soma diameter = 43.4 microns) and rostral bulbar gigantocellular tegmental field (41.3 microns) gave rise to reticulospinal fibers descending in the ipsilateral medial longitudinal fasciculus and ventral funiculus and distributed in laminae V-X with an ipsilateral predominance. These were primarily large-diameter fibers. (2) Predominantly large neurons (46.9 microns) in the bulbar gigantocellular tegmental field gave rise to reticulospinal fibers descending in the contralateral medial longitudinal fasciculus and ventral funiculus. These were mainly large-diameter fibers. (3) Neurons of predominantly medium size (29.5 microns) in the pontine gigantocellular tegmental field gave rise to reticuloreticular fibers descending directly to and distributed bilaterally in the bulbar reticular formation. These were small-diameter fibers. (4) Neurons of predominantly medium size (28.9 microns) in the bulbar gigantocellular tegmental field gave rise to reticulospinal fibers descending in the ipsilateral reticular formation and lateral funiculus. These were small-diameter fibers.

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)