Morphology of vertical canal related second order vestibular neurons in the cat

Summary The morphology of vertical canal related second order vestibular neurons in the cat was studied with the intracellular horseradish peroxidase method. Neurons were identified by their monosynaptic potentials following electrical stimulation via bipolar electrodes implanted into individual semicircular canal ampullae. Anterior and posterior canal neurons projected primarily to contralateral or ipsilateral motoneuron pools (excitatory and inhibitory pathways, respectively). The axons of contralaterally projecting neurons crossed the midline at the level of the abducens nucleus and bifurcated into an ascending and a descending main branch which travelled in the medial longitudinal fasciculus (MLF). Two types of anterior canal neurons were observed, one with unilateral and one with bilateral oculomotor projection sites. For both neuron classes, the major termination sites were in the. contralateral superior rectus and inferior oblique subdivisions of the oculomotor nucleus. In neurons which terminated bilaterally, major collaterals recrossed the midline within the oculomotor nucleus to reach the ipsilateral superior rectus motoneuron pool. Other, less extensive, termination sites of both neuron classes were in the contralateral vestibular nuclear complex, the facial nucleus, the medullary and pontine reticular formation, midline areas within and neighboring the raphé nuclei, and the trochlear nucleus. The ascending main axons continued further rostrally to reach the interstitial nucleus of Cajal and areas around the fasciculus retroflexus. The descending branches proceeded further caudal in the medial vestibulo-spinal tract but were not followed to their spinal target areas. In addition to two previously described posterior canal related neuron types (Graf et al. 1983), we found neurons with bilateral oculomotor terminals and a spinal collateral. Typical for posterior canal neurons, the major termination sites were in the trochlear nucleus (superior oblique motoneurons) and in the inferior rectus subdivision of the oculomotor nucleus. Axon collaterals recrossed the midline to reach ipsilateral inferior rectus motoneurons. The axons of ipsilaterally projecting neurons ascended through the reticular formation to join the MLF caudal to the trochlear nucleus. The main target sites of anterior canal related neurons were in the trochlear nucleus and the inferior rectus subdivision of the oculomotor nucleus. Minor collaterals reached the pontine reticular formation and areas in between the fiber bundles of the ipsilateral MLF. In some cases, small collaterals crossed the midline within the oculomotor nucleus to terminate in the inferior rectus subdivision on the contralateral side. The axon proceeded further rostral to project to the interstitial nucleus of Cajal and beyond. The main termination sites of posterior canal neurons were in the superior rectus and inferior oblique subdivisions of the oculomotor nucleus. Minor collaterals were also observed to reach the midline area within the oculomotor nucleus, however, prospective contralateral termination sites could not be identified. More rostral projections were found in the interstitial nucleus of Cajal. The described axonal arborization of second order vestibular neurons reflects the organization of intrinsic coordinate systems as exemplified by the geometry of the semicircular canal and the extraocular muscle planes. These neurons are interpreted to provide a matrix for coordinate system transformation, i.e. from vestibular into oculomotor reference frames, and to play a role in gaze control and related reflexes by distributing their signals to multiple termination sites.Abbreviations DV descending vestibular nucleus - INC interstitial nucleus of Cajal - INT nucleus intercalatus - IQ inferior oblique subdivision - LV lateral vestibular nucleus - MLF medial longitudinal fasciculus - MRF medullary reticular formation - MV medial vestibular nucleus - nVII facial nerve - PH nucleus praepositus hypoglossi - PRF pontine reticular formation - RO nucleus Roller - SR superior rectus subdivision - SV superior vestibular nucleus - III oculomotor nucleus - IV trochlear nucleus - VI abducens nucleus - VII facial nucleus - XII hypoglossal nucleus Supported by NIH grants EY04613 and NS02619     

The vestibuloocular reflex of the adult flatfish. II. Vestibulooculomotor connectivity

The peripheral and central oculomotor organization of the adult flatfish presents no morphological substrates that suffice to explain adaptive changes in its vestibuloocular reflex system. The necessity for an adaptation occurs because of a 90 degrees displacement of the vestibular with respect to the extraocular coordinate axes during metamorphosis. Since a reorganization of vestibuloocular pathways must be hypothesized (12), the location and termination of electrophysiologically identified secondary vestibular neurons with focus on the horizontal canal system was studied with the intracellular horseradish peroxidase method in adult winter flounders. Pseudopleuronectes americanus. The oculomotor target sites of vertical canal related neurons were similar to those described in mammals. Presumed excitatory anterior canal neurons bifurcated after the main axon had crossed the midline. The descending branch headed toward the spinal cord. The ascending branch reached the oculomotor nucleus via the contralateral medial longitudinal fasciculus and terminated in the superior rectus and inferior oblique subdivisions. Presumed inhibitory posterior canal neurons ascended ipsilaterally in the medial longitudinal fasciculus and terminated mainly in the superior rectus and inferior oblique subdivisions. Horizontal canal neurons exhibited characteristics distinctly different from mammalian ones. Two types of second-order neurons were observed. In the first case, cell bodies were located in the anterior portion of the vestibular nuclear complex. After crossing the midline, the axon ascended in the contralateral medial longitudinal fasciculus. Major termination sites were found in the inferior oblique and superior rectus subdivisions of the oculomotor nucleus. Axonal branches then recrossed the midline and terminated in identical locations on the ipsilateral side. In the second case, cell bodies were located in the descending vestibular nucleus. Their axons crossed the midline and also ascended in the contralateral medial longitudinal fasciculus. Major termination sites were in the trochlear nucleus and in the inferior rectus subdivision of the oculomotor nucleus. As in the first case, axonal branches also recrossed the midline and terminated in identical motoneuron pools on the ipsilateral side. The above target sites were exactly those expected to be used in a reciprocal excitatory-inhibitory fashion during compensatory eye movements. Head-down movement would be excitatory for the lower horizontal canal producing contractions of both superior recti and inferior obliques as well as relaxation of the antagonistic inferior recti and superior obliques.(ABSTRACT TRUNCATED AT 400 WORDS)     

Morphology of posterior canal related secondary vestibular neurons in rabbit and cat

The morphology of secondary vertical vestibular neurons was investigated by injection of horseradish peroxidase (HRP) into cells connected to the posterior canal system in rabbits (lateral-eyed animals) and cats (frontal-eyed animals). Vestibular neurons were identified by stimulation with bipolar electrodes implanted into the ampullae of the anterior and posterior (PC) semicircular canals of pigmented rabbits; in the cat, these cells were identified by natural and electrical stimulation. Axons monosynaptically activated by PC stimulation were injected with HRP in the medial longitudinal fasciculus (MLF). These were later reconstructed by light microscopy after the brains had been processed with a DAB-CoCl2 method. In the rabbit the majority of the axons bifurcated after crossing the midline with one branch ascending and the other descending in the MLF. The ascending branches gave rise to collaterals that terminated in both the trochlear nucleus and the inferior rectus subdivision of the oculomotor nucleus. In addition some axons also sent collaterals into the paramedian pontine reticular formation, the periaqueductal grey and the interstitial nucleus of Cajal. The descending branches were followed to the caudal part of the medulla in the MLF and gave rise to collaterals terminating in the vestibular nuclei, the medullary reticular formation, the perihypoglossal nuclei, the abducens nucleus, and the facial nucleus. In another cell type axons crossed the midline without giving off any collaterals and proceeded caudally in the caudal MLF. The synaptic effects of the two types of cells were concluded to be excitatory and inhibitory, respectively. Cell bodies of contralaterally projecting neurons were located in either the medial or ventro-lateral vestibular nuclei. In the cat we observed two neuron classes, with contralaterally projecting axons, whose synaptic effects are presumably excitatory. Their cell somata were located in the medial vestibular nucleus. Termination patterns were similar to both the trochlear and oculomotor nuclei, but neither projected to the abducens nucleus. One class of neurons was almost identical to that found in the rabbit with the main axon bifurcating in the MLF. The second type lacked a descending branch in the MLF. Axon collaterals of the latter type crossed the midline within the oculomotor nucleus after terminating in the inferior rectus subdivision to reach a similar portion of the ipsilateral oculomotor nucleus. Collaterals of these axons also terminated bilaterally in the supraoculomotor region between trochlear and oculomotor nucleus, the interstitial nucleus of Cajal and prerubral loci (including the fields of Forel). In similarity to the rabbit, presumed inhibitory vestibular neurons were found with axons directed caudally in the MLF without brain stem collaterals.(ABSTRACT TRUNCATED AT 400 WORDS)     

Vertical eye movement-related secondary vestibular neurons ascending in medial longitudinal fasciculus in cat. II. Direct connections with extraocular motoneurons

1. The preceding study in the alert cat has shown that many secondary vestibular axons that ascend in the medial longitudinal fasciculus (MLF) increase their firing rate in proportion to downward eye position. In the present study, projection and termination of these downward-position-vestibular (DPV) neurons within extraocular motoneuron pools were studied electrophysiologically by spike-triggered averaging techniques and morphologically be reconstructing their axonal trajectory after intra-axonal injection of horseradish peroxidase (HRP). 2. Extracellular field potentials recorded within the trochlear nucleus and/or the inferior rectus subdivision of the oculomotor nucleus were averaged by the use of spike potentials of single DPV neurons as triggers. All the crossed-DPV axons tested induced negative unitary field potentials in the trochlear nucleus (n = 9) and in the inferior rectus subdivision of the oculomotor nucleus (n = 5), suggesting that they made monosynaptic excitatory connection with motoneurons in these nuclei. The four crossed-DPV axons tested in the two motoneuron pools induced unitary field potentials in both. The majority of crossed-DPV axons terminated in these nuclei were directly activated from the caudal MLF, indicating that they had descending collaterals projecting to the spinal cord as well. The uncrossed-DPV axons did not induce such unitary field potentials either in the trochlear nucleus (n = 4) or in the inferior rectus subdivision (n = 3). 3. All the uncrossed-DPV axons examined (n = 14) induced positive unitary field potentials in the superior rectus subdivision of the oculomotor nucleus, suggesting that they made monosynaptic inhibitory connections with motoneurons innervating the superior rectus muscle. These uncrossed-DPV axons displayed regular firing patterns and were not activated from the caudal MLF. None of the crossed-DPV axons tested (n = 4) induced unitary field potentials in the superior rectus subdivision. 4. Five crossed-DPV axons were injected with HRP. All these axons ascended in the MLF contralateral to their soma, gave off many collaterals to the trochlear nucleus, and projected more rostrally. For three well-stained axons, numerous terminal branches were also found in the rostroventral part of the contralateral oculomotor nucleus, the area corresponding to the inferior rectus subdivision. Some collaterals in the oculomotor nucleus recrossed the midline to terminate in the medial part of the ipsilateral oculomotor nucleus. Other terminations were observed in the interstitial nucleus of Cajal and in the periaqueductal gray adjacent to the oculomotor nucleus. The crossed axons injected included both regular and irregular types, and three of the four examined were activated from the caudal MLF.(ABSTRACT TRUNCATED AT 400 WORDS)     

Operational unit responsible for plane-specific control of eye movement by cerebellar flocculus in cat

1. Main findings in our previous studies are as follows: 1) there are three Purkinje cell zones running perpendicular to the long axis of the folia in the cat flocculus, 2) the caudal zone controls activity of the superior rectus (SR) and inferior oblique (IO) extraocular muscles via the y-group and oculomotor nucleus (OMN) neurons, and 3) the middle zone controls activity of the lateral (LR) and medial rectus (MR) muscles via the medial vestibular (MV) and abducens nucleus (ABN) neurons. In the present study, the neuronal pathways from the remaining rostral zone were investigated in the anesthetized cat. 2. Target neurons of rostral zone inhibition in the superior vestibular nucleus (SV) were identified by observing cessation of spontaneous discharges after rostral zone stimulation. Efferent projections were studied by the use of systematic microstimulation techniques. Unitary responses to stimulation of the eighth nerves were also investigated. 3. There are two types of the target neurons: 1) those, being located in the central and dorsal parts of the SV, project to the trochlear and oculomotor nuclei innervating superior oblique and inferior rectus muscles via the ipsilateral medial longitudinal fasciculus (MLF); and 2) those, being located along the dorsal border of the SV, project to the contralateral oculomotor nucleus innervating superior rectus and inferior oblique muscles via the extra-MLF route. 4. Both types receive monosynaptic anterior canal nerve input but not posterior canal nerve input. Some neurons receive polysynaptic excitatory input from the contralateral eighth nerve, although commissural inhibition was never observed. 5. From neuronal connections of the rostral and caudal zones and action of the extraocular muscles, it was expected that 1) activity changes of Purkinje cells in the rostral and/or caudal zones on one side resulted in conjugate eye movement in the plane of the anterior canal on the side of the activity changes, 2) cooperative increased activity on both sides resulted in conjugate downward eye movement, and 3) increased activity on one side and decreased activity on the other side resulted in conjugate rotatory eye movement. The rostral and caudal zones may be responsible for eye-movement control in the sagittal plane by cooperative activity changes on both sides and in the transverse plane by reciprocal activity changes on both sides. For eye-movement control in the anterior canal plane, Purkinje cell activity on one side would be sufficient to produce the required movement. In a functional sense, we call the rostral and caudal zones, the vertical-plane zones.(ABSTRACT TRUNCATED AT 400 WORDS)     

Spatial properties of second-order vestibulo-ocular relay neurons in the alert cat

Second-order vestibular nucleus neurons which were antidromically activated from the region of the oculomotor nucleus (second-order vestibuloocular relay neurons) were studied in alert cats during whole-body rotations in many horizontal and vertical planes. Sinusoidal rotation elicited sinusoidal modulation of firing rates except during rotation in a clearly defined null plane. Response gain (spike/s/deg/s) varied as a cosine function of the orientation of the cat with respect to a horizontal rotation axis, and phases were near that of head velocity, suggesting linear summation of canal inputs. A maximum activation direction (MAD) was calculated for each cell to represent the axis of rotation in three-dimensional space for which the cell responded maximally. Second-order vestibuloocular neurons divided into 3 non-overlapping populations of MADs, indicating primary canal input from either anterior, posterior or horizontal semicircular canal (AC, PC, HC cells). 80/84 neurons received primary canal input from ipsilateral vertical canals. Of these, at least 6 received input from more than one vertical canal, suggested by MAD azimuths which were sufficiently misaligned with their primary canal. In addition, 21/80 received convergent input from a horizontal canal, with about equal number of type I and type II yaw responses. 4/84 neurons were HC cells; all of them received convergent input from at least one vertical canal. Activity of many vertical second-order vestibuloocular neurons was also related to vertical and/or horizontal eye position. All AC and PC cells that had vertical eye position sensitivity had upward and downward on-directions, respectively. A number of PC cells had MADs centered around the MAD of the superior oblique muscle, and 2/3 AC cells recorded in the superior vestibular nucleus had MADs near that of the inferior oblique. Thus, signals with spatial properties appropriate to activate oblique eye muscles are present at the second-order vestibular neuron level. In contrast, none of the second-order vestibuloocular neurons had MADs near those of the superior or inferior rectus muscles. Signals appropriate to activate these eye muscles might be produced by combining signals from ipsilateral and contralateral AC neurons (for superior rectus) or PC neurons (for inferior rectus). Alternatively, less direct pathways such as those involving third or higher order vestibular or interstitial nucleus of Cajal neurons might play a crucial role in the spatial transformations between semicircular canals and vertical rectus eye muscles.     

Structure of the primate oculomotor burst generator. I. Medium-lead burst neurons with upward on-directions

1. To investigate the structure of the primate burst generator for vertical saccades, we obtained intra-axonal records from vertical medium-lead burst neurons with upward on-directions (UMLBs) in alert, behaving squirrel monkeys, while monitoring their spontaneous eye movements. After physiological characterization, these UMLBs were injected with horseradish peroxidase. 2. UMLBs (n = 14) had no spontaneous activity and emitted bursts of action potentials that preceded rapid eye movements by approximately 6 ms. Parameters of the burst (duration and number of spikes) were highly correlated with parameters of the rapid eye movement (duration and amplitude of the upward displacement of the eyes). 3. The axons of six UMLBs projected to the oculomotor complex. Their somata (4 were recovered) were all in the rostral interstitial nucleus of the medial longitudinal fasciculus (riMLF). Their axons traveled caudally in the medial longitudinal fasciculus (MLF) and ramified in the interstitial nucleus of Cajal (NIC) before entering the oculomotor nucleus. Five axons terminated bilaterally in the subdivisions innervating the superior rectus and inferior oblique muscles and therefore were presumed to be excitatory. One axon terminated in the ipsilateral inferior rectus and superior oblique subdivisions of the oculomotor complex and was presumed to be inhibitory. 4. Additionally, our data demonstrate that the nucleus of the posterior commissure (nPC) may also contain UMLBs. The axon of one such neuron crossed the midline within the posterior commissure and provided terminal fields to the contralateral nPC, riMLF, NIC, and the mesencephalic reticular formation but not to the oculomotor complex. 5. In conclusion, our data demonstrate that the rostral mesencephalon of the monkey contains neurons that have both the activity and the connections that are necessary either to provide motoneurons innervating extraocular muscles of both eyes with the pulse of activity they display during upward saccades or to inhibit their antagonists. Furthermore, our data demonstrate that some UMLBs are better suited for closing the feedback path of the local feedback loop rather than for providing direct input to extraocular motoneurons.     

Arborization of axons in oculomotor nucleus identified by vestibular stimulation and intra-axonal injection of horseradish peroxidase

Summary Axons in the medial rectus (MR) subdivisions of the oculomotor nucleus were identified by horizontal rotation and by electrical stimulation of the vestibular nerves and abducens nuclei. Three types of axons (vestibular type I and II and abducens interneurons) were then injected intra-axonally with horseradish peroxidase (HRP). Each injected axon was reconstructed under the microscope in the frontal and horizontal planes and terminal arborization and boutons contacting with MR motoneurons were studied. The MR motoneurons were identified by retrograde uptake of HRP, HRP being injected in the MR muscle prior to the intra-axonal experiment.The main types of horizontal canal-related axons were as follows: (1) ATD-unilateral termination axons: Most type I axons were of this type. Axons ascended in ascending tract of Deiters (ATD) to the oculomotor nucleus and terminated in ipsilateral MR area. (2) ATD-bilateral termination axons: Very few secondary canal responsive axons were in this group. Axons ascended in ATD to the oculomotor nucleus and terminated in MR motoneuron areas bilaterally and in the Edinger-Westphal nucleus. (3) MLF-bilateral termination axons: Most type II neurons were in this group. Axons went up in the contralateral MLF and into both oculomotor nuclei. Their branches distributed to several motoneuron areas but only infrequently to the MR area; and to the Edinger-Westphal nucleus. (4) AB interneuron axons: Axons ascended in the MLF contralateral to cells of origin and terminated in the contralateral MR motoneuron area.Supported by USPHS Grant No. 06658     

Pathways for the vestibulo-ocular reflex excitation arising from semicircular canals of rabbits

Summary In anesthetized albino rabbits, ampullary branches of the vestibular nerve were stimulated electrically. Prominent and stable reflex contraction was induced in extra-ocular muscles by applying single current pulses of relatively long duration, 3–5 msec. Survey with a glass microelectrode revealed that, during application of relatively wide pulses to a canal, primary vestibular fibers discharged impulses repetitively at a rate as high as 300–1400/sec and that after being transmitted across second-order vestibular neurons these impulses built up summated EPSPs in oculomotor neurons, large enough to trigger off motoneuronal discharges. From each semicircular canal, prominent reflex contraction was evoked selectively in two muscles; from the anterior canal in the ipsilateral superior rectus and contralateral inferior oblique; from the horizontal canal in the ipsilateral medial rectus and contralateral lateral rectus; and from the posterior canal in the ipsilateral superior oblique and contralateral inferior rectus. Acute lesion experiments indicated that signals for this excitation reached IIIrd and IVth nuclei via three different pathways; from the anterior canal through the ipsilateral brachium conjunctivum, from the horizontal canal through the ipsilateral fasciculus longitudinalis medialis and from the posterior canal through the contralateral fasciculus longitudinalis medialis.This work was supported by a grant from Educational Ministry of Japan (844021).     

Axon collaterals to the extraocular motoneuron pools of inhibitory vestibuloocular neurons activated from the anterior, posterior and horizontal semicircular canals in the cat

The branching pattern of inhibitory vestibuloocular neurons and their synaptic contacts with extraocular motoneurons were studied by means of spike-triggered averaging and local stimulation techniques. Individual vestibuloocular neurons activated by stimulation of the ampullary nerve of the anterior semicircular canal (ACN) inhibited motoneurons in both the ipsilateral (i-) trochlear nucleus and i-inferior rectus motoneuron pools. Individual vestibuloocular neurons receiving input from the ampullary nerve of the posterior semicircular canal (PCN) inhibited motoneurons in both the i-inferior oblique and i-superior rectus motoneuron pools. Probably, these axonal trajectories underlie conjugate eye movement during vertical head rotation. No conclusive evidence was found to indicate that single inhibitory vestibular neurons receiving input from the horizontal semicircular canal (HCN) give off axon collaterals to the i-abducens and the contralateral medial rectus motoneurons. A separate projection of HCN-related neurons to motoneurons supplying the lateral and medial rectus muscles might be useful for convergence during horizontal head movement.     

Excitatory input from interneurons in the abducens nucleus to medial rectus motoneurons mediating conjugate horizontal nystagmus in the cat

Summary A class of interneurons in the cat abducens nucleus was identified by its antidromic activation from the contralateral ascending MLF, disynaptic activation from the contralateral vestibular nerve and type II response to rotation of the turntable. They were also activated antidromically from the contralateral oculomotor nucleus, the region of medial rectus motoneurons. Extracellular spikes of single interneurons, spontaneous or glutamate-driven, were used as triggers for perior post-spike averaging of three kinds of potentials. (1) The average of the extracellular field potentials within the contralateral oculomotor nucleus consisted of an early positive or positive-negative spike and a late, slow negative wave. The early spike was an action current caused by impulses along the axon of the interneuron. The late potential was the extracellular counterpart of unitary EPSPs. (2) The averaged membrane potential of contralateral medial rectus motoneurons revealed unitary EPSPs with monosynaptic latencies, evidence that interneurons were excitatory in nature. (3) The average of compound potentials of the contralateral medial rectus nerve showed a monosynaptic excitatory effect relevant to unitary EPSPs. This effect was observed with nearly all interneurons. All interneurons thus identified exhibited discharge patterns closely correlated with the activity of medial rectus motoneurons in both slow and quick phases of vestibular nystagmus. It was concluded that these interneurons controlled activities of contralateral medial rectus motoneurons associated with conjugate horizontal eye movements by their monosynaptic excitatory connections.     

Collateralization of cerebellar efferent projections to the paraoculomotor region,superior colliculus,and medial pontine reticular formation in the rat: a fluorescent double-labeling study

Summary Collateralization of cerebellar efferent projections to the oculomotor region, superior colliculus (SC), and medial pontine reticular formation (mPRF) was studied in rats using fluorescent tracer substances. In one group, True Blue (TB) was injected into the oculomotor complex (OMC), including certain paraoculomotor nuclei and supraoculomotor ventral periaqueductal gray (PAG), and Diamidino Yellow (DY) was injected into the medial pontine reticular formation (mPRF) or pontine raphe. The largest number of single-TB-labeled (paraoculomotor-projecting) cells was observed in the medial cerebellar nucleus (MCN) and posterior interposed nucleus (PIN), whereas the largest number of single-DY-labeled (mPRF-projecting) cells was in the MCN. Double-TB/DY-labeled cells were present in the caudal two-thirds of the MCN, suggesting that some MCN neurons send divergent axon collaterals to the paraoculomotor region and mPRF. In another group, TB was injected into the SC and DY into the mPRF. The largest number of single-TB-labeled (SC-projecting) cells was in the PIN, although a considerable number of cells was observed in the caudal MCN, and ventral lateral cerebellar nucleus (LCN). Single-DY-labeled (mPRF-projecting) neurons were primarily located in the central and ventral MCN, but were also present in the lateral anterior interposed (AIN) and in the LCN. Double-TB/DY-labeled neurons were observed in the caudal two-thirds of the MCN and in the central portion of the LCN. The most significant new findings of the study concerned the MCN, which not only contained neurons that projected independently to the paraoculomotor region, SC, and mPRF, but also contained a considerable number of cells which collateralized to project to more than one of these nuclei. The possibility that the MCN projects to the supraoculomotor ventral PAG (containing an oculomotor interneuron system) and to the mPRF, which in the cat and monkey contain neural elements essential to the production of saccadic eye movements, is discussed. The anatomical findings suggest that the MCN in the rat plays an important role in eye movement.Abbreviations AI anterior interposed nucleus - AIN anterior interposed nucleus - BC brachium conjunctivum (sup. cerebellar peduncle) - dlh dorsolateral hump of the AI - dmc dorsomedial crest of the AI - IC inferior colliculus - ICP inferior cerebellar peduncle - Inf infracerebellar nucleus - L lateral cerebellar (dentate) nucleus - LCN lateral cerebellar (dentate) nucleus - M medial cerebellar (fastigial) nucleus - MCN medial cerebellar (fastigial) nucleus - MLF medial longitudinal fasciculus - mPRF medial pontine reticular formation (incl. nuc. reticularis pontis oralis and caudalis) - OMC oculomotor complex - OMN oculomotor nucleus - PI posterior interposed nucleus - PIN posterior interposed nucleus - RN red nucleus - SC superior colliculus - Vl lateral vestibular nucleus - Vs superior vestibular nucleus - Y cell group Y     

The time course of retrograde transsynaptic transport of tetanus toxin fragment C in the oculomotor system of the rabbit after injection into extraocular eye muscles

Summary The aim of this study was to determine the optimal survival time for labelling those neurons that monosynaptically terminate on extraocular motoneurons, i.e. the premotor neurons, after an injection of tetanus toxin fragment C, a retrograde transsynaptic tracer substance, into the eye muscle of the rabbit. Concentrated fragment C was injected into the inferior rectus or inferior oblique muscle and detected immunocytochemically in the brain after survival times of 8 h, 17 h, 2 d, 3 d, 4 d, 5 d, 6 d, 8 d and 12 d. Immunoreactivity was confined to granules within motoneuronal and premotor neuronal cell bodies, but became associated with punctate profiles outlining the somata with longer survival times. The strongest and most consistent labelling of premotor cell bodies was seen after 4 days survival time. The transsynaptic labelling pattern was shown to vary for individual premotor pathways.Abbreviations III oculomotor nucleus - IV trochlear nucleus - Vmes mesencephalic trigeminal nucleus - Vmt motor trigeminal nucleus - VI abducens nucleus - VIacc accessory abducens nucleus - VII facial nucleus - BC brachium conjunctivum, co cochlear nucleus - CR restiform body - d dentate nucleus - DAB diamino-benzidine-tetrahydrochloride - HRP horseradish peroxidase - iC interstitital nucleus of Cajal, iv inferior vestibular nucleus - lgn_d lateral geniculate nucleus dorsalis - lgn_v lateral geniculate nucleus ventralis - lv lateral vestibular nucleus - mgn medial geniculate nucleus - MLF medial longitudinal fasciculus - mv_p medial vestibular nucleus pars parvocellularis - mv_m medial vestibular nucleus pars magnocellularis (= ventral part of the lv) - NIII oculomotor nerve - NV trigeminal nerve - NVII facial nerve - NVIII vestibular nerve - PC posterior commissure - pg periaquaeductal grey - ppH nucleus praepositus hypoglossi - riMLF rostral interstitial nucleus of the medial longitudinal fasciculus - rn red nucleus - sc superior colliculus - sn substantia nigra - so superior olive - sv superior vestibular nucleus - sv_c superior vestibular nucleus contralateral - sv_i superior vestibular nucleus ipsilateral - TR tractus retroflexus - Y Y-group zi zona incerta     

Directional sensitivity of anterior, posterior, and horizontal canal vestibulo-ocular neurons in the cat

Neurons subserving the vestibulo-ocular reflex transform the directionality and timing of input from semicircular canals into commands that are appropriate to rotate the eyes in a compensatory fashion. In order to assess the degree to which this transformation is evident in vestibular nucleus neurons of alert cats, we recorded the extracellular discharge properties of 138 second-order vestibular neurons in the superior and medial vestibular nucleus, including 64 neurons identified as second-order vestibulo-ocular neurons by antidromic responses to oculomotor nucleus stimulation and short-latency orthodromic responses to labyrinth stimulation (1.3 ms or less). Neuronal response gains and phases were recorded during 0.5-Hz sinusoidal oscillations about many different horizontal axes and during vertical axis rotations to define neuronal response directionality more precisely than in past studies. Neurons with spatial responses similar to anterior semicircular canal afferents were found to have more diverse maximal activation direction vectors than neurons with responses resembling those of posterior or horizontal canal afferents. The mean angle from neuron response vector to the axis of the nearest canal or canal pair was 19 degrees for anterior canal second-order neurons (n=28) and 20 degrees for anterior canal second-order vestibulo-ocular neurons (n=18), compared with 11 degrees for posterior canal second-order neurons (n=43) and 11 degrees for posterior canal second-order vestibulo-ocular neurons (n=25). Only two second-order vestibulo-ocular neurons (3%) showed a marked dependence of response phase on rotation direction, which is indicative of convergent inputs that differ in both dynamics and directionality. This suggests that spatiotemporal convergence is uncommon in the three-neuron vestibulo-ocular reflex arc of the cat. Neuron vectors included many that were closely aligned with canal axes and several that were better aligned with oblique or superior rectus extraocular muscle excitation axis vectors. Only single examples of second-order vestibulo-ocular neuron vectors were approximately aligned with the pitch and roll coordinate axes. We conclude that second-order vestibulo-ocular neurons do not exclusively represent either the semicircular canal sensory coordinate frame or the extraocular muscle excitation motor coordinate frame, and instead are mostly distributed on a continuum between the input and output coordinate frames, with anterior canal neurons having the widest distribution of directionality.     

A note on the development of the vestibulo-ocular pathway in the chicken

Summary The vestibulo-ocular pathways have been examined in embryonic chicks using horseradish peroxidase or dil as retrograde and anterograde tracers. The vestibular neurons project to the rostral, external eye motor nuclei over one or the other of three separate pathways; the ipsilateral and controlateral medial longitudinal fascicle and the contralateral brachium conjunctivum. The brachium conjunctivum component originates dorsally in the superior vestibular region and projects to the contralateral inferior oblique and superior rectus motor nuclei. An ipsilateral component of the medial longitudinal fascicle is labeled from more ventral sites in the vestibulo-cerebellar process and terminates in the ipsilateral superior oblique and inferior rectus nuclei. The contralateral medial longitudinal fascicle component originates still more ventrally and terminates in the contralateral superior oblique and inferior rectus motor nuclei. Accordingly, the vestibulo-ocular pathways in chickens operate predominantly on synergistic pairs of external eye muscles. These selective terminal fields are established within a day or two after the first terminals invade the eye motor nuclei during embryo-genesis.Abbreviations Br.C. brachium conjunctivum - EW Edinger Westfahl nucleus - MLF medial longitudinal fascicle - IO inferior oblique muscle - RI inferior rectus muscle - RM medial rectus muscle - RS superior rectus muscle - SO superior oblique muscle - V-O vestibular-ocular - i ipsilateral - x contralateral This paper is dedicated to Professor Fred Walberg on the occasion of his 70th birthday     

Branching pattern and properties of vertical- and horizontal-related excitatory vestibuloocular neurons in the cat

1. The axonal trajectories of excitatory vestibuloocular neurons and their synaptic contacts with extraocular motoneurons were studied by means of spike-triggered signal averaging and microstimulation techniques. A majority of the excitatory neurons related to the vertical semicircular canals were located in the border of the descending and medial nuclei and the rostral half of the descending nucleus. 2. Individual vestibuloocular neurons activated by stimulation of the ampullary nerve of the anterior semicircular canal excited motoneurons within both the contralateral inferior oblique and contralateral superior rectus motoneuron pools. 3. Individual vestibuloocular neurons receiving input from the ampullary nerve of the posterior semicircular canal excited motoneurons in both the contralateral trochlear nucleus and contralateral inferior rectus motoneuron pools. The branching pattern of single vestibuloocular neurons activated by the anterior and posterior canals probably underlies conjugate eye movement during vertical head rotation. 4. Time to peak and shape indices of unitary excitatory postsynaptic potentials (EPSPs) suggested that the location of the synaptic contact of vestibuloocular neurons was on the soma or proximal dendrites of the target extraocular motoneurons. 5. In contrast, we did not find conclusive evidence that single vestibuloocular neurons receiving input from the horizontal semicircular canal give off axon collaterals to motoneurons innervating both the contralateral lateral rectus and the ipsilateral medial rectus muscles. Projection of horizontal vestibuloocular neurons to motoneurons supplying individual muscles might be useful for convergence during horizontal head movement.     

Development of the amphibian oculomotor complex: Evidences for migration of oculomotor motoneurons across the midline

Summary The development of the oculomotor nucleus in five species of salamanders and one anuran species was investigated with tracing techniques. The data presented support the hypothesis that oculomotor motoneurons innervating the superior rectus muscle migrate across the midline. In the salamander Pleurodeles waltl, only ipsilateral oculomotor motoneurons are labeled in early development. Later, these neurons extend dendrites toward the contralateral side into the ventral tegmental neuropil, after which there is displacement of their nuclei (neuronal somata) across the midline. Cell bodies can be observed directly at the midline. In adult Salamandra salamandra, motoneurons innervating the superior rectus muscle are seen occasionally at the midline and on the ipsilateral side, with dendrites toward the contralateral side. Motoneurons on the ipsilateral side do not display these features. In Pleurodeles, developmental brain processes are slowed down, and the sequence of development of the contralateral subnucleus, which can be clearly observed, supports the migration hypothesis. In Xenopus laevis and most other species of salamanders this process is accelerated.     

Two groups of secondary vestibular neurons mediating horizontal canal signals, probably to the ipsilateral medial rectus muscle, under inhibitory influences from the cerebellar flocculus in rabbits

Vestibular nuclear neurons that mediate horizontal canal signals to the ipsilateral medial rectus motoneurons were explored in anesthetized and decerebrate rabbits. These neurons were identified by four criteria: (1) they were activated monosynaptically by ipsilateral vestibular nerve stimulation and (2) antidromically from the oculomotor nucleus region, while they were inhibited by (3) direct floccular stimulation and (4) ipsilateral retinal stimulation that activated floccular Purkinje cells via a climbing fiber afferent pathway. Neurons fulfilling these criteria were found in two anatomically different regions, i.e. the rostrolateral part of the medial vestibular nucleus and in the ventral part of the lateral vestibular nucleus. In decerebrate rabbits, neurons in both loci responded to horizontal rotation of the whole body with the type I pattern (excited by ipsilateral rotation). These results suggest that horizontal canal signals are conveyed to ipsilateral medial rectus motoneurons by two separate groups of vestibular nuclear neurons which may play different roles in the vestibulo-ocular reflex.     

Morphophysiological study on the divergent projection of axon collaterals of medial vestibular nucleus neurons in the cat

(1) Spikes of single neurons were extracellularly recorded in the medial vestibular nucleus (MVN) in decerebrate cats and were functionally identified as secondary type I neurons by observing their responses to horizontal rotation and monosynaptic activation after stimulation of the ipsilateral vestibular nerve. Axonal projection of these neurons was examined by their antidromic responses to stimulation of the contralateral abducens nucleus, the spinal cord, and the ascending and descending MLF. (2) Almost all secondary type I vestibular neurons which sent their axon to the contralateral abducens nucleus were antidromically activated from the descending MLF at the level of the obex as well. Nearly half of these neurons sent their collateral axon to the level of C1 segment in the spinal cord and approximately one third to the ascending MLF close to the oculomotor complex. (3) The mean conduction velocity was 29 m/s for descending collateral axons and 30 m/s for ascending collateral axons. (4) Systematic tracking for antidromic microstimulation in the contralateral abducens nucleus and spinal gray matter at C2-C3 suggested that collateral axons of single type I vestibular neurons gave off local branches in the abducens nucleus and the motoneuron pool in the upper cervical gray matter. Existence of terminal branches in the neck motoneuron pool was confirmed by intraaxonal staining with horseradish peroxidase (HRP). (5) Neurons which projected to both the contralateral abducens nucleus and the spinal cord were located in a fairly localized region in the ventrolateral part of the rostral MVN. Neurons which projected to the contralateral abducens nucleus and not to the spinal cord were located in a rostrocaudally wider area in the ventrolateral MVN. Neurons projecting to the spinal cord and not to the contralateral abducens nucleus were located in the widest area in the rostrocaudal direction, covering almost the whole extent of the rostral half of the MVN.     

Vestibular projections to the nuclei of the extraocular muscles Degeneration resulting from discrete partial lesions of the vestibular nuclei in the monkey

In 35 monkeys attempts were made to produce localized unilateral lesions in individual vestibular nuclei in order to study vestibular projections to nuclei of the extraocular muscles. Portions of the medial, superior and inferior vestibular nuclei were destroyed selectively; lesions in Deiters' nucleus involved small portions of either the superior or inferior vestibular nuclei. Fiber degeneration was studied by the Nauta-Gygax technic. Exclusively ascending fibers from the superior vestibular nucleus project to ipsilateral extraocular nuclei. Ascending fibers from the inferior vestibular arise only from rostral portions of the nucleus, are not numerous and pass to all extraocular nuclei. The medial vestibular nucleus projects ascending fibers via the MLF bilaterally, asymmetrically and differentially to all extraocular nuclei. Prominent projections pass to: (a) the contralateral trochlear nucleus, and (b) the contralateral intermediate cell column and the ipsilateral ventral nucleus of the oculomotor complex. Ascending fibers from Deiters' nucleus, arising only from ventral portions of the nucleus, project primarily to: (a) the contralateral abducens and trochlear nuclei, and (b) specific asymmetrical portions of the oculomotor complex. Ascending vestibular fibers from the medial and lateral vestibular nuclei appear capable of mediating all patterned eye movements resulting from stimulation of ampullary nerves from individual semicircular canals. Vestibular projections to nuclei of the extraocular muscles are most abundant to those nuclei innervating muscles whose primary functions concern horizontal and rotatory eye movements.