Gradual and reversible central vestibular reorganization in frog after selective labyrinthine nerve branch lesions

Postlesional reorganization of vestibular afferent and commissural inputs onto second-order vestibular neurons was studied in the isolated brain after unilateral section of the N.VIII, of the ramus anterior (RA) of N.VIII, of the utricular (UT) or of the anterior vertical and horizontal canal nerves in combination. RA nerve section eliminated the inputs from utricular, anterior vertical and horizontal canal organs. In the first set of experiments we recorded field potentials on the operated side of the vestibular nuclei 2 months after RA nerve section. These responses were evoked by electrical stimulation of the RA nerve or of the posterior vertical canal nerve on the operated or on the intact side. The amplitudes of afferent field potentials evoked by stimulation of the spared posterior vertical canal nerve were increased. The amplitudes of afferent field potentials evoked by stimulation of the axotomized RA nerve remained unaltered. After N.VIII section the commissural, but not the afferent, field potentials increased significantly on the operated side following stimulation of N.VIII on the intact and on the operated side, respectively. After UT nerve section no change in commissural but an increase in the amplitude of afferent field potentials from each of the three intact canal nerves was observed on the operated side. In the context of earlier results these findings imply that second-order vestibular neurons, disfacilitated due to afferent nerve section, became receptive to additional, excitatory synaptic inputs, preferentially from intact vestibular nerve afferent fibers. The reduced excitation via afferent nerve inputs was thereby replaced by other afferent nerve inputs from spatially inadequate vestibular end-organs. The synaptic terminals of inactivated afferent nerve fibers were maintained and not repressed. The process of central reorganization after vestibular nerve lesion was activity related, the expansion of signals restricted to inputs from intact fibers, its extent graded and its onset delayed with respect to the onset of corresponding spinal changes and to the onset of postural recovery after the same type of nerve lesion. After the section of RA nerve or of an individual nerve branch the labyrinthine end-organs remained intact and were not removed as after unilateral labyrinthectomy (UL). Peripheral reinnervation of the end-organs was thus excluded after UL, but expected after one of the former types of lesion. Functional reinnervation of the utricular macula was mirrored behaviorally by the reappearance of severe postural deficits following a second RA nerve section. These lesion-induced postural deficits began to reappear if the repeated RA nerve section was delayed with respect to the first by about 3 months. We therefore studied postlesional reorganization in the brainstem 3 months after the first RA nerve section. Reinnervation of the utricular macula was accompanied by a rapid decline of the increased amplitudes of afferent and commissural vestibular field potentials towards control values, suggesting the reversibility of the lesion-induced central reorganization. Electronic Publication     

Expansion of afferent vestibular signals after the section of one of the vestibular nerve branches

The anterior branch of N. VIII was sectioned in adult frogs. Two months later the brain was isolated to record in vitro responses in the vestibular nuclei and from the abducens nerves following electric stimulation of the anterior branch of N. VIII or of the posterior canal nerve. Extra- and intracellularly recorded responses from the intact and operated side were compared with responses from controls. Major changes were detected on the operated side: the amplitudes of posterior canal nerve evoked field potentials were enlarged, the number of vestibular neurons with a monosynaptic input from the posterior canal nerve had increased, and posterior canal nerve stimulation recruited stronger abducens nerve responses on the intact side than vice versa. Changes in the convergence pattern of vestibular nerve afferent inputs on the operated side strongly suggest the expansion of posterior canal-related afferent inputs onto part of those vestibular neurons that were deprived of their afferent vestibular input. As a mechanism we suggest reactive synaptogenesis between intact posterior canal afferent fibers and vestibularly deprived second-order vestibular neurons.     

Plane-specific brainstem commissural inhibition in frog second-order semicircular canal neurons

Commissural inputs of identified second-order semicircular canal neurons were studied by separate stimulation of each of the three canal nerves on either side in the vitro frog brains. The spatial pattern of these inputs was further investigated in those second-order canal neurons that received a monosynaptic input from only one ipsilateral canal nerve (91%). Since similar results were obtained in the presence as in the absence of the cerebellum, commissural inputs must have been relayed via fibers crossing in the brainstem. Following stimulation of individual semicircular canal nerves, commissural inputs were either inhibitory or excitatory. A commissural inhibition was evoked in the majority of the recorded neurons (79%) by stimulation of the coplanar semicircular canal nerve on the contralateral side. In the remaining neurons, a commissural excitatory input was evoked. A commissural excitation, originating from the two noncoplanar semicircular canals, predominated in most (68%) of the recorded neurons and was independent of the type of second-order canal neuron. The onset latency of the canal plane-specific commissural inhibitory potentials was di- or trisynaptic. Stimulation of the contralateral VIIIth nerve evoked excitatory commissural responses. The canal plane-specific commissural inhibition therefore might have been masked by commissural excitatory responses as in earlier studies. The similar organization of the canal plane-specific commissural inhibition in frog and cat corroborates the notion of a phylogenetically conservative, basic vestibular organization. The presence of a canal plane-unspecific commissural excitation, however, appears to be a feature that is specific to frogs. The functional implications of these similarities and differences are discussed.     

Postlesional vestibular reorganization improves the gain but impairs the spatial tuning of the maculo-ocular reflex in frogs

The ramus anterior (RA) of N.VIII was sectioned unilaterally. Two months later we analyzed in vivo responses of the ipsi- and of the contralesional abducens nerve during horizontal and vertical linear acceleration in darkness. The contralesional abducens nerve had become responsive again to linear acceleration either because of a synaptic reorganization in the vestibular nuclei on the operated side and/or because of a reinnervation of the utricular macula by regenerating afferent nerve fibers. Significant differences in the onset latencies and in the acceleration sensitivities allowed a separation of RA frogs in a group without and in a group with functional utricular reinnervation. Most important, the vector orientation for maximal abducens nerve responses was clearly altered: postlesional synaptic reorganization resulted in the emergence of abducens nerve responses to vertical linear acceleration, a response component that was barely detectable in RA frogs with utricular reinnervation and that was absent in controls. The ipsilesional abducens nerve, however, exhibited unaltered responses in either group of RA frogs. The altered spatial tuning properties of contralesional abducens nerve responses are a direct consequence of the postlesional expansion of signals from intact afferent nerve and excitatory commissural fibers onto disfacilitated 2nd-order vestibular neurons on the operated side. These results corroborate the notion that postlesional vestibular reorganization activates a basic neural reaction pattern with more beneficial results at the cellular than at the network level. However, given that the underlying mechanism is activity-related, rehabilitative training after vestibular nerve lesion can be expected to shape the ongoing reorganization.     

Properties of utricular-activated vestibular neurons that project to the contralateral vestibular nuclei in the cat

The properties of utricular (UT)-activated vestibular neurons that send axons to the contralateral vestibular nuclei (commissural neurons) were investigated intracellularly or extracellularly in decerebrate cats. A total of 27 vestibular neurons were orthodromically activated by stimulation of UT nerves and antidromically activated by stimulation of the contralateral vestibular nuclei. All neurons tested were classified as vestibulospinal (VS), vestibulooculospinal (VOS), vestibuloocular (VO), and unidentified vestibular neurons (V) after antidromic stimulation of the spinal cord and oculomotor/trochlear nuclei. Most UT-activated commissural neurons (20/27) received monosynaptic inputs. Twelve of 27 commissural neurons were located in the medial vestibular nucleus, 5 were in the lateral vestibular nucleus, 10 were in the descending vestibular nucleus, and no commissural neurons were recorded in the superior vestibular nucleus. Seven of 27 neurons were commissural VS neurons, 9 of 27 were commissural VOS neurons, and 11 of 27 were commissural V neurons. No commissural VO neurons were found. All VOS neurons and 3 VS neurons issued descending axons via the medial vestibulospinal tract. We also studied convergent inputs from the posterior semicircular canal (PC) nerve onto UT-activated commissural neurons. Five of 27 UT-activated commissural neurons received converging inputs from the PC nerves. Electronic Publication     

Vestibulo-reticular projections in adult lamprey: their role in locomotion

This study describes the anatomical projections from vestibular secondary neurons to reticulospinal neurons in the adult lamprey and the modulation of vestibular inputs during fictive locomotion. Anatomical tracers were applied in the posterior (PRRN) and middle rhombencephalic reticular nuclei as well as to the proximal stumps of cut vestibular nerve branches to identify the neurons projecting to the reticular nuclei that were in close proximity with vestibular primary afferents. Labeled neurons were found in the intermediate (ION) and posterior (PON) octavomotor nuclei, and were more numerous on the side of the injection (around 56-87 and 101-107 for the ION and the PON, respectively). Morphologies varied but cells were mostly round or oval. Axonal projections from the PON formed a dense bundle, whereas those from the ION were less densely packed. Based on their morphology and the distribution of their projections, most vestibulo-reticular neurons were presumed to be vestibulospinal cells. Reticulospinal cells from the PRRN were recorded intracellularly in the in vitro brainstem-spinal cord preparation and large excitatory post-synaptic potentials (EPSPs) were evoked following stimulation of the ipsilateral anterior and the contralateral posterior branches of the vestibular nerves, whereas inhibitory post-synaptic potentials (IPSPs) or smaller EPSPs were elicited by stimulation of the ipsilateral posterior or of the contralateral anterior branches. During fictive locomotion, both the excitatory and the inhibitory responses displayed phasic changes in amplitude such that the amplitude of the EPSPs was minimal when the spinal cord activity switched from the ipsilateral to the contralateral side of the recorded reticulospinal cell. The IPSPs were then of maximal amplitude. We propose that this modulation could serve to reduce the influence of vestibular inputs in response to head movements during locomotion.     

Topographic representation of vestibular and somatosensory signals in the anuran thalamus

In the isolated brain of the fire-bellied toad, Bombina orientalis, the spatial distribution of vestibular and somatosensory responses in thalamic nuclei was studied following electrical activation of the Vth nerve, the ramus anterior of the VIIIth nerve and of the dorsal roots of spinal nerves 3 and 8. Responses were systematically mapped in frontal planes through the diencephalon at four rostro-caudal levels. The calculated activity maps were superimposed on the outlines of diencephalic nuclei, and those nuclei that received particularly large inputs from the stimulated sensory nerve roots were indicated. Maximal response amplitudes coincided with ventral, central, and posterior thalamic areas and exhibited a topography that differed for each sensory nerve root. Maximal responses evoked from the Vth nerve were largely separated from those from spinal dorsal roots 3 and 8, whereas maximal vestibular responses partly overlapped with those from the other somatosensory nerve roots. Our findings indicate that within the amphibian thalamus sensory signals originating from different nerve roots are largely represented in separate areas as is the case in the thalamus of amniotes. However, the anterior dorsal thalamus which is the only origin of ascending pathways to the medial and dorsal pallium (assumed homologues of the mammalian hippocampus and neocortex, respectively) receives only minor vestibular and somatosensory input. This corroborates the view that amphibians lack a direct sensory thalamo-cortical, or "lemnothalamic," pathway typical of mammals and birds.     

Commissural inputs to secondary vestibular neurons in alert cats after canal plugs

Gaze is stabilized during head movements primarily by the vestibuloocular reflex (VOR). After a unilateral canal plug, the VOR's response is reduced. Recovery of the VOR may be brought about by changes in the efficacy of brain stem synapses or by other mechanisms. We measured the responses of horizontal secondary vestibular neurons (HSNs) to stimulation of the contralateral labyrinth. HSN responses in normal alert cats were compared with those in cats that had recovered from unilateral horizontal semicircular canal (HSCC) plugs. After recovery, excitatory commissural inputs to HSNs on the plugged side elicited significantly smaller responses than in normal cats with no change in mean discharge rates. However, mean discharge rates tended to be higher after recovery for cells receiving inhibitory commissural inputs. The change in resting rate invalidates any direct comparison of inhibitory inputs. These results are interpreted in terms of possible mechanisms for recovery from unilateral vestibular loss by the VOR neural network. We conclude that after unilateral HSCC plugs, changes in brain stem excitatory synapses and/or excitability of secondary vestibular neurons may participate in the restoration of normal vestibular reflexes.     

The commissural inhibition on secondary vestibulo-ocular neurons in the vertical semicircular canal systems in the cat

The commissural inhibition on secondary vestibulo-ocular neurons (VOns) from the contralateral (c-) vertical canal system in the same geometric plane was studied in the anesthetized cat. The secondary VOns were identified by their orthodromic responses to stimulation of the ampullary nerves of the anterior (ACN) or posterior (PCN) semicircular canals and also by their antidromic responses to stimulation of the IIIrd and IVth nuclei. The majority of ACN-activated excitatory VOns in the descending and medial nuclei (32/36, 89%) and in the superior nucleus (20/23, 87%), received commissural inhibition from the c-PCN, while only few ACN-activated inhibitory VOns (3/35, 9%) in the superior nucleus received commissural inhibition from the c-PCN. On the other hand, all of the PCN-activated excitatory (50/50) and inhibitory (30/30) VOns in the vestibular nuclei received commissural inhibition following c-ACN stimulation.     

Basic organization principles of the VOR: lessons from frogs

Locomotion is associated with a number of optical consequences that degrade visual information processing in the absence of appropriate compensatory movements. The resulting retinal image flow is counteracted by coordinated eye-head reflexes that are initiated by optokinetic and vestibular inputs. The contribution of the vestibulo-ocular reflex (VOR) for stabilizing retinal images is relatively small in amplitude in frogs but important in function by compensating for the non-linearities of the neck motor system. The spatial tuning of the VOR networks underlying the angular (AVOR) and linear (LVOR) with respect to canal and extraocular motor coordinates is organized in a common, canal-related reference frame. Thereby, the axes of head and eye rotation are aligned, principle and auxiliary VOR connections transform vestibular into motor signals and parallel AVOR and LVOR circuits mediate vergence and version signals separately. Comparison of these results with data from other vertebrates demonstrates a number of fundamental organization principles common to most vertebrates. However, the fewer degrees of behavioral freedom of frogs are reflected by the absence of, e.g. a functioning velocity storage network or of a fixation suppression of the VOR. In vitro experiments with the isolated brainstem and branches of N.VIII attached were used to study the putative transmitters of vestibular nerve afferent inputs, the postsynaptic receptor subtypes of second-order vestibular neurons and their dynamic response properties. Evidence is presented that suggests that afferent vestibular nerve fibers with different dynamic response properties activate different subtypes of glutamate receptors. The convergence pattern of monosynaptic afferent nerve inputs from different labyrinthine organs onto second-order vestibular neurons is remarkably specific. As a rule, second-order vestibular neurons receive converging afferent nerve inputs from one semicircular canal and from a specific sector of hair cells on one otolith organ. This convergence pattern remains malleable even in adulthood and reorganization is initiated by activity-related changes in vestibular nerve afferent fibers. The output of second-order vestibular neurons is modified by at least three inhibitory control loops. Uncrossed inhibitory vestibular side loops appear to control specifically the dynamic response tuning, whereas coplanar commissural inhibitory inputs improve mainly the spatial tuning and the cerebellar feedback loop controls the response gain. Among the targets of second-order vestibular projection neurons are extraocular motoneurons and internuclear neurons. Extraocular motoneurons differ among each other by the presence of very different response dynamics. These differences may represent a co-adaptation to the response dynamics of twitch and non-twitch extraocular muscle fibers. Different dynamical properties are required for a rapid acceleration of the globe at the one end and for the maintenance of a stable eccentric eye position over long periods of time at the other end of a continuum of variations in dynamic response properties. The maintenance of a given eccentric eye position over long periods of time is especially well developed in frogs and assists visual surveillance during lurking in the absence of saccades.     

Plastic changes underlying vestibular compensation in the guinea-pig persist in isolated, in vitro whole brain preparations.

Vestibular compensation for the postural and oculomotor deficits induced by unilateral labyrinthectomy is a model of post-lesional plasticity in the central nervous system. Just after the removal of one labyrinth, the deafferented, ipsilateral vestibular nucleus neurons are almost silent, and the discharge of the contralateral vestibular nucleus neurons is increased. The associated static disorders disappear in a few days, as normal activity is restored in both vestibular nuclei. In this study, we searched for traces of vestibular compensation in isolated whole brains taken from adult guinea-pigs. The electrophysiological responses evoked in control brains were compared to those evoked in brains taken from animals that had previously been labyrinthectomized. Guinea-pigs compensated for an initial labyrinthectomy within three days. In vivo, subsequent deafferentation of vestibular nucleus neurons on the intact side triggered "Bechterew's phenomenon": a new postural and oculomotor syndrome appeared, similar to the one induced by the first lesion, but directed to the newly deafferented side. These disturbances would be caused by the new imbalance between the discharges of neurons in the two vestibular nuclei triggered by the second deafferentation. Experiments were designed to search for a similar imbalance in vitro in brains taken from labyrinthectomized animals, where the intact vestibular nerve is cut during the dissection. Isolated whole brains were obtained from young guinea-pigs at various times (one to seven days) following an initial labyrinthectomy. An imbalance between the resting activities of medial vestibular nucleus neurons on both sides of the brainstem was revealed in brains taken more than three days after the lesion: their discharge was higher on the compensated, initially lesioned side than on the newly deafferented side. In some cases, an oscillatory pattern of discharge, reminiscent of the spontaneous nystagmus associated in vivo with Bechterew's syndrome, appeared in both abducens nerves. These data demonstrate that most of the changes underlying vestibular compensation persist, and can thus be investigated in the isolated whole brain preparation. Brains removed only one day after the lesion displayed normal commissural responses and symmetric spinal inputs to vestibular nucleus neurons. However, an unusually large proportion of the neurons recorded on both sides of the preparation had very irregular spontaneous discharge rates. These data suggest that the first stages of vestibular compensation might be associated with transient changes in the membrane properties of vestibular nucleus neurons. Brains taken from compensated animals displayed a significant, bilateral decrease of the inhibitory commissural responses evoked in the medial vestibular nucleus by single-shock stimulation of the contralateral vestibular nerve. The sensitivity of abducens motoneurons on the initially lesioned, compensated side to synaptic activation from the contralesional vestibular nucleus neurons was also decreased. Both changes may explain the long-term, bilateral decrease of vestibular-related reflexes observed following unilateral labyrinthectomy. Spinal inputs to vestibular nucleus neurons became progressively asymmetric: their efficacy was increased on the lesioned side and decreased on the intact one. This last modification may support a functional substitution of the deficient, vestibular-related synergies involved in gaze and posture stabilization by neck-related reflexes.     

Tonic influence of the efferent vestibular system on the spontaneous afferent activity from semicircular canals in the frog (Rana esculenta L.)

Summary In the frog we have recorded the spontaneous activity of single afferent fibres of the ampullary nerves of the left horizontal semicircular canal (HC) and vertical anterior canal (VAC) in isolated head preparations. The recordings have been made in 4 experimental situations: intact preparations; preparations whose brain was destroyed; preparations whose contralateral vestibular nerve had been cut between Scarpa's ganglion and the brain; preparations where either an ampullary nerve (that of the HC or of the VAC) or the utricular nerve had been cut contralaterally. From our results, it appears that the efferent vestibular system has a tonic influence on the afferent activity from HC and VAC; the influence of the part of the efferent vestibular system (EVS) activity depending on contralateral vestibular inputs is inhibitory, while the influence of the part of the EVS activity depending on ipsilateral vestibular inputs might be facilitatory.     

Otolith and canal integration on single vestibular neurons in cats

In this review, based primarily on work from our laboratory, but related to previous studies, we summarize what is known about the convergence of vestibular afferent inputs onto single vestibular neurons activated by selective stimulation of individual vestibular nerve branches. Horizontal semicircular canal (HC), anterior semicircular canal (AC), posterior semicircular canal (PC), utricular (UT), and saccular (SAC) nerves were selectively stimulated in decerebrate cats. All recorded neurons were classified as either projection neurons, which consisted of vestibulospinal (VS), vestibulo-oculospinal (VOS), vestibulo-ocular (VO) neurons, or non-projection neurons, which we simply term vestibular (V) neurons. The first three types could be successfully activated antidromically from oculomotor/trochlear nuclei and/or spinal cord, and the last type could not be activated antidromically from either site. A total of 1228 neurons were activated by stimulation of various nerve pair combinations. Convergent neurons were located in the caudoventral part of the lateral, the rostral part of the descending, and the medial vestibular nuclei. Otolith-activated vestibular neurons in the superior vestibular nucleus were extremely rare. A high percentage of neurons received excitatory inputs from two nerve pairs, a small percentage received reciprocal convergent inputs and even fewer received inhibitory inputs from both nerves. More than 30% of vestibular neurons received convergent inputs from vertical semicircular canal/otolith nerve pairs. In contrast, only half as many received convergent inputs from HC/otolith-nerve pairs, implying that convergent input from vertical semicircular canal and otolith-nerve pairs may play a more important role than that played by inputs from horizontal semicircular canal and otolith-nerve pairs. Convergent VS neurons projected through the ipsilateral lateral vestibulospinal tract (i-LVST) and the medial vestibulospinal tract (MVST). Almost all the VOS neurons projected through the MVST. Convergent neurons projecting to the oculomotor/trochlear nuclei were much fewer in number than those projecting to the spinal cord. Some of the convergent neurons that receive both canal and otolith input may contribute to the short-latency pathway of the vestibulocollic reflex. The functional significance of these convergences is discussed.     

The effects of stimulating the cerebellar nodulus in the cat on the responses of vestibular neurons

In a first series of experiments, recordings were obtained from cat abducens and trochlear motorneurons and from axons of secondary vestibular neurons terminating in these motor nuclei, and the effects of cerebellar nodulus stimulation on utricular- and canal-evoked responses in these neurons were studied. Ultricular activation of vestibular axons recorded in the ipsilateral VIth and contralateral IVth nuclei was probably monosynaptically inhibited by nodular stimulation provided conditioning-test intervals were in the range between 0-10 ms and the test stimuli were close to threshold intensities. Of the vestibular axons activated by stimulation of the semicircular canal nerves only those evoked by the horizontal canal stimulation and recorded in the ipsilateral VIth nucleus were weakly inhibited. When the vestibular stimuli were strong enough to produce clear field potentials in the motor nuclei and/or postsynaptic potentials in motorneurons, nodular stimulation had practically no effect on their amplitudes. It is concluded that inhibition of vestibuloocular transmission is weak as compared to floccular inhibition studied previously. In a second series of experiments, recordings were obtained from vestibular neurons which were activated antidromically and/or transsynaptically by stimulation of the contralateral fastigial nucleus, and the effects of ipsilateral nodular stimulation on these responses were studied. It was found that nodular stimulation inhibited both antidromic as well as transsynaptic fastigial activations of vestibular neurons. Most of these vestibular neurons were located in the descending vestibular nucleus and received polysynaptic vestibular and spinal inputs. It is concluded that in addition to its weak inhibitory effect on vestibuloocular transmission the nodulus exerts a powerful inhibition on vestibular neurons transmitting vestibular and spinal inputs to cerebellar nuclei and/or cortex. It is suggested that the nodulus controls cerebellar projecting vestibular neurons which carry vestibular and spinal information to the cerebellum. The vestibular, proprioceptive and visual information which is present in the nodulus may aid the role of the nodulus in controlling body posture.     

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.     

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).     

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)     

Convergence pattern of uncrossed excitatory and inhibitory semicircular canal-specific inputs onto second-order vestibular neurons of frogs

Second-order vestibular neurons of frogs receive converging monosynaptic excitatory and disynaptic excitatory and inhibitory inputs following electrical pulse stimulation of an individual semicircular canal nerve on the ipsilateral side. Here we revealed, in the in vitro frog brain, disynaptic inhibitory postsynaptic potentials (IPSPs) by bath application of antagonists specific for glycine or gamma-aminobutyric acid-A (GABA(A)) receptors. Differences in the response parameters between disynaptic IPSPs and excitatory postsynaptic potentials (EPSPs) suggested that disynaptic IPSPs originated from a more homogeneous subpopulation of thicker vestibular nerve afferent fibers than mono- or disynaptic EPSPs. To investigate a possible size-related organization of these canal-specific, parallel pathways, we combined long-lasting anodal currents of variable intensities with strong cathodal test pulses, to block pulse-evoked responses reversibly in a graded manner according to the size-related sensitivity of vestibular nerve afferent fibers. The anodal current intensity required to block a particular response component was about 15 times lower than the strength of the cathodal test pulse that activated this response component. These large threshold differences were exploited for a selective anodal suppression of the responses from thick vestibular nerve afferent fibers. In fact, response components known to originate exclusively from thick-caliber afferent fibers such as the electrically transmitted monosynaptic EPSP component exhibited the lowest thresholds for cathodal test pulses and were the first to disappear in the presence of small anodal polarization steps. Thresholds for the activation/inactivation of responses and current intensities required for response saturation/blockade were used to assess the fiber spectrum that evoked the different response components. Mono- and disynaptic EPSPs appeared to originate from a broad spectrum of thick and thin vestibular nerve afferent fibers. The spectrum of afferent fibers that activated disynaptic IPSPs on the other hand was more homogeneous and consisted of thick and intermediate fibers. Such a canal-specific and fiber type-related organization of converging inputs of second-order vestibular neurons via feedforward projections was shown for the first time by this study in frogs, but might also prevail in mammals. Similar differences in these feedforward pathways have been proposed earlier in a vestibular side-loop model. Our results are consistent with the basic assumptions of this model and relate to the processing and tuning of dynamic vestibular signals.     

Superior vestibular nucleus neurones related to the excitatory vestibulo-ocular reflex of anterior canal origin and their ascending course in the cat

Stimulation of the superior vestibular nucleus and the anterior canal nerve evoked mono- and disynaptic excitatory postsynaptic potentials, respectively, in contralateral inferior oblique motoneurones of the cat. Combined stimulation revealed that the superior vestibular nucleus relayed excitatory anterior canal signals to the motoneurones. Thirty-six superior vestibular neurones receiving anterior canal inputs were activated antidromically by microstimulation of the contralateral inferior oblique motoneurone pool. Their axons ascended neither in the brachium conjunctivum nor in the medial longitudinal fasciculus, but proceeded rostrally in the ventral part of the brain stem.     

Patterns of canal and otolith afferent input convergence in frog second-order vestibular neurons

Second-order vestibular neurons (2 degrees VN) were identified in the isolated frog brain by the presence of monosynaptic excitatory postsynaptic potentials (EPSPs) after separate electrical stimulation of individual vestibular nerve branches. Combinations of one macular and the three semicircular canal nerve branches or combinations of two macular nerve branches were stimulated separately in different sets of experiments. Monosynaptic EPSPs evoked from the utricle or from the lagena converged with monosynaptic EPSPs from one of the three semicircular canal organs in ~30% of 2 degrees VN. Utricular afferent signals converged predominantly with horizontal canal afferent signals (74%), and lagenar afferent signals converged with anterior vertical (63%) or posterior vertical (37%) but not with horizontal canal afferent signals. This convergence pattern correlates with the coactivation of particular combinations of canal and otolith organs during natural head movements. A convergence of afferent saccular and canal signals was restricted to very few 2 degrees VN (3%). In contrast to the considerable number of 2 degrees VN that received an afferent input from the utricle or the lagena as well as from one of the three canal nerves (~30%), smaller numbers of 2 degrees VN (14% of each type of 2 degrees otolith or 2 degrees canal neuron) received an afferent input from only one particular otolith organ or from only one particular semicircular canal organ. Even fewer 2 degrees VN received an afferent input from more than one semicircular canal or from more than one otolith nerve (~7% each). Among 2 degrees VN with afferent inputs from more than one otolith nerve, an afferent saccular nerve input was particularly rare (4-5%). The restricted convergence of afferent saccular inputs with other afferent otolith or canal inputs as well as the termination pattern of saccular afferent fibers are compatible with a substrate vibration sensitivity of this otolith organ in frog. The ascending and/or descending projections of identified 2 degrees VN were determined by the presence of antidromic spikes. 2 degrees VN mediating afferent utricular and/or semicircular canal nerve signals had ascending and/or descending axons. 2 degrees VN mediating afferent lagenar or saccular nerve signals had descending but no ascending axons. The latter result is consistent with the absence of short-latency macular signals on extraocular motoneurons during vertical linear acceleration. Comparison of data from frog and cat demonstrated the presence of a similar organization pattern of maculo- and canal-ocular reflexes in both species.