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.     

Evidence for corrective effects of afferent signals from the extraocular muscles on single units in the pigeon vestibulo-oculomotor system

The role of extraocular muscle (EOM) afferent feedback signals in the control of eye movement is still controversial. We recorded from 106 single units in the vestibular nuclei, oculomotor nuclei and reticular formation of 80 decerebrate, paralysed pigeons. EOM afferents were stimulated by passive eye movement (PEM) during vestibular stimulation by sinusoidal oscillation in the horizontal plane. We found that EOM afferent signals profoundly modified the vestibular responses of 91 (86%) of the single units recorded. As well as using PEM to simulate eye movements similar to saccades, we moved the eye in a manner which mimicked the slow phase of the vestibulo-ocular reflex (artificial VOR, AVOR). We have found evidence that, as well as providing signals closely related to the parameters of eye movement, PEM alters the vestibular responses of cells during AVOR in a manner which suggests that EOM afferent signals may play a corrective role in the moment-to-moment control of eye movement in the vestibulo-ocular reflex.     

Effects of viewing distance on the responses of horizontal canal-related secondary vestibular neurons during angular head rotation.

Effects of viewing distance on the responses of horizontal canal-related secondary vestibular neurons during angular head rotation. The eye movements generated by the horizontal canal-related angular vestibuloocular reflex (AVOR) depend on the distance of the image from the head and the axis of head rotation. The effects of viewing distance on the responses of 105 horizontal canal-related central vestibular neurons were examined in two squirrel monkeys that were trained to fixate small, earth-stationary targets at different distances (10 and 150 cm) from their eyes. The majority of these cells (77/105) were identified as secondary vestibular neurons by synaptic activation following electrical stimulation of the vestibular nerve. All of the viewing distance-sensitive units were also sensitive to eye movements in the absence of head movements. Some classes of eye movement-related vestibular units were more sensitive to viewing distance than others. For example, the average increase in rotational gain (discharge rate/head velocity) of position-vestibular-pause units was 20%, whereas the gain increase of eye-head-velocity units was 44%. The concomitant change in gain of the AVOR was 11%. Near viewing responses of units phase lagged the responses they generated during far target viewing by 6-25 degrees. A similar phase lag was not observed in either the near AVOR eye movements or in the firing behavior of burst-position units in the vestibular nuclei whose firing behavior was only related to eye movements. The viewing distance-related increase in the evoked eye movements and in the rotational gain of all unit classes declined progressively as stimulus frequency increased from 0.7 to 4.0 Hz. When monkeys canceled their VOR by fixating head-stationary targets, the responses recorded during near and far target viewing were comparable. However, the viewing distance-related response changes exhibited by central units were not directly attributable to the eye movement signals they generated. Subtraction of static eye position signals reduced, but did not abolish viewing distance gain changes in most units. Smooth pursuit eye velocity sensitivity and viewing distance sensitivity were not well correlated. We conclude that the central premotor pathways that mediate the AVOR also mediate viewing distance-related changes in the reflex. Because irregular vestibular nerve afferents are necessary for viewing distance-related gain changes in the AVOR, we suggest that a central estimate of viewing distance is used to parametrically modify vestibular afferent inputs to secondary vestibuloocular reflex pathways.     

Physiological and behavioral identification of vestibular nucleus neurons mediating the horizontal vestibuloocular reflex in trained rhesus monkeys.

1. To describe in detail the secondary neurons of the horizontal vestibuloocular reflex (VOR), we recorded the extracellular activity of neurons in the rostral medial vestibular nucleus of alert, trained rhesus monkeys. On the basis of their activity during horizontal head and eye movements, neurons were divided into several different types. Position-vestibular-pause (PVP) units discharged in relation to head velocity, eye velocity, eye position, and ceased firing during some saccades. Eye and head velocity (EHV) units discharged in relation to eye velocity and head velocity in the same direction so that the two signals partially canceled during the VOR. Two cell types discharged in relation to eye position and velocity but not head velocity; other types discharged in relation to head velocity only. 2. The position in the neural path from the primary vestibular afferents to abducens motoneurons was examined for each type. Direct input from the vestibular nerve was indicated if the cell could be activated by shocks to the nerve at latencies less than or equal to 1.4 ms. A projection to abducens motoneurons was indicated if spike-triggered averaging of lateral rectus electromyographic (EMG) activity yielded responses with a sharp onset at monosynaptic latencies. 3. PVP neurons were the principal interneuron in the VOR "three-neuron arc." Eighty percent received primary afferent input, and 66% made excitatory connections with contralateral abducens motoneurons. Surprisingly few, approximately 11%, made inhibitory connections with ipsilateral abducens motoneurons. This imbalance in the ipsi- and contralateral projections was confirmed by measuring the EMG activity evoked by electrical microstimulation in regions where PVP neurons were located. 4. EHV neurons whose activity increased during contralaterally directed head or eye movements were also interneurons in the ipsilateral inhibitory pathway. Eighty-nine percent received ipsilateral primary afferent input, and 25% projected to ipsilateral abducens motoneurons. EHV neurons excited during ipsilateral movements received neither direct primary afferent input nor projected to either abducens nucleus. A small proportion of each of two other cell types having sensitivity to contralateral eye position made excitatory connections with contralateral abducens motoneurons. Other types rarely were activated from the eighth nerve or projected to the abducens nucleus. 5. The significance of the connections of VOR interneurons and the signals they convey is discussed for three situations: smooth pursuit of a moving target, suppression of the VOR, and the VOR itself. PVP neurons convey a signal with a ratio of eye position and velocity components that is inappropriate to drive motoneurons during pursuit or the VOR.(ABSTRACT TRUNCATED AT 400 WORDS)     

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.     

Effects of viewing distance on the responses of vestibular neurons to combined angular and linear vestibular stimulation.

Effects of viewing distance on the responses of vestibular neurons to combined angular and linear vestibular stimulation. The firing behavior of 59 horizontal canal-related secondary vestibular neurons was studied in alert squirrel monkeys during the combined angular and linear vestibuloocular reflex (CVOR). The CVOR was evoked by positioning the animal's head 20 cm in front of, or behind, the axis of rotation during whole body rotation (0.7, 1.9, and 4.0 Hz). The effect of viewing distance was studied by having the monkeys fixate small targets that were either near (10 cm) or far (1.3-1.7 m) from the eyes. Most units (50/59) were sensitive to eye movements and were monosynaptically activated after electrical stimulation of the vestibular nerve (51/56 tested). The responses of eye movement-related units were significantly affected by viewing distance. The viewing distance-related change in response gain of many eye-head-velocity and burst-position units was comparable with the change in eye movement gain. On the other hand, position-vestibular-pause units were approximately half as sensitive to changes in viewing distance as were eye movements. The sensitivity of units to the linear vestibuloocular reflex (LVOR) was estimated by subtraction of angular vestibuloocular reflex (AVOR)-related responses recorded with the head in the center of the axis of rotation from CVOR responses. During far target viewing, unit sensitivity to linear translation was small, but during near target viewing the firing rate of many units was strongly modulated. The LVOR responses and viewing distance-related LVOR responses of most units were nearly in phase with linear head velocity. The signals generated by secondary vestibular units during voluntary cancellation of the AVOR and CVOR were comparable. However, unit sensitivity to linear translation and angular rotation were not well correlated either during far or near target viewing. Unit LVOR responses were also not well correlated with their sensitivity to smooth pursuit eye movements or their sensitivity to viewing distance during the AVOR. On the other hand there was a significant correlation between static eye position sensitivity and sensitivity to viewing distance. We conclude that secondary horizontal canal-related vestibuloocular pathways are an important part of the premotor neural substrate that produces the LVOR. The otolith sensory signals that appear on these pathways have been spatially and temporally transformed to match the angular eye movement commands required to stabilize images at different distances. We suggest that this transformation may be performed by the circuits related to temporal integration of the LVOR.     

Postlesional vestibular reorganization in frogs: evidence for a basic reaction pattern after nerve injury

Nerve injury induces a reorganization of subcortical and cortical sensory or motor maps in mammals. A similar process, vestibular plasticity 2 mo after unilateral section of the ramus anterior of N. VIII was examined in this study in adult frogs. The brain was isolated with the branches of both N. VIII attached. Monosynaptic afferent responses were recorded in the vestibular nuclei on the operated side following ipsilateral electric stimulation either of the sectioned ramus anterior of N. VIII or of the intact posterior vertical canal nerve. Excitatory and inhibitory commissural responses were evoked by separate stimulation of each of the contralateral canal nerves in second-order vestibular neurons. The afferent and commissural responses of posterior vertical canal neurons recorded on the operated side were not altered. However, posterior canal-related afferent inputs had expanded onto part of the deprived ramus anterior neurons. Inhibitory commissural responses evoked from canal nerves on the intact side were detected in significantly fewer deprived ramus anterior neurons than in controls, but excitatory commissural inputs from the three contralateral canal nerves had expanded. This reactivation might facilitate the survival of deprived neurons and reduce the asymmetry in bilateral resting activities but implies a deterioration of the original spatial response tuning. Extensive similarities at the synaptic and network level were noted between this vestibular reorganization and the postlesional cortical and subcortical reorganization of sensory representations in mammals. We therefore suggest that nerve injury activates a fundamental neural reaction pattern that is common between sensory modalities and vertebrate species.     

Sacculo-ocular reflex connectivity in cats

The otolith system contributes to the vestibulo-ocular reflexes (VOR) when the head moves linearly in the horizontal plane or tilts relative to gravity. The saccules are thought to detect predominantly accelerations along the gravity vector. Otolith-induced vertical eye movements following vertical linear accelerations are attributed to the saccules. However, information on the neural circuits of the sacculo-ocular system is limited, and the effects of saccular inputs on extraocular motoneurons remain unclear. In the present study, synaptic responses to saccular-nerve stimulation were recorded intracellularly from identified motoneurons of all twelve extraocular muscles. Experiments were successfully performed in eleven cats. Individual motoneurons of the twelve extraocular muscles--the bilateral superior recti (SR), inferior recti (IR), superior obliques (SO), inferior obliques (IO), lateral recti (LR), and medial recti (MR) were identified antidromically following bipolar stimulation of their respective nerves. The saccular nerve was selectively stimulated by a pair of tungsten electrodes after removing the utricular nerve and the ampullary nerves of the semicircular canals. Stimulus intensities were determined from the stimulus-response curves of vestibular N1 field potentials in order to avoid current spread. Intracellular recordings were performed from 129 extraocular motoneurons. The majority of the neurons showed no response to saccular-nerve stimulation. In 17 (30%) of 56 extraocular motoneurons related to vertical eye movements (bilateral SR and IR), depolarizing and/or hyperpolarizing postsynaptic potentials (PSPs) were observed in response to saccular-nerve stimulation. The latencies of PSPs ranged from 2.3 to 8.9 ms, indicating that the extraocular motoneurons received neither monosynaptic nor disynaptic inputs from saccular afferents. The majority of the latencies of the depolarization, including depolarization-hyperpolarization, were in the range of 2.3-3.3 ms. Latencies of hyperpolarizations were typically longer than those of depolarizations. Only one contralateral SO motoneuron of 43 recorded oblique extraocular motoneurons (bilateral SO and IO) showed a depolarization-hyperpolarization in response to saccular-nerve stimulation at a latency of 2.5 ms. None of 30 recorded horizontal extraocular motoneurons (bilateral LR and MR) responded to stimulation of the saccular nerve. The neural linkage in the sacculo-ocular system is relatively weak in comparison to the utriculo-ocular and sacculo-collic systems, suggesting that the role of the sacculo-ocular system in stabilizing eye position may be reduced when compared with utriculo-ocular and semi-circular canal-ocular reflexes.     

Canal-otolith interactions in the squirrel monkey vestibulo-ocular reflex and the influence of fixation distance

Natural head movements include angular and linear components of motion. Two classes of vestibulo-ocular reflex (VOR), mediated by the semicircular canals and otoliths (the angular and linear VOR, or AVOR and LVOR, respectively), compensate for head movements and help maintain binocular fixation on targets in space. In this study, AVOR/LVOR interactions were quantified during complex head motion over a broad range of fixation distances at a fixed stimulus frequency of 4.0 Hz. Binocular eye movements were recorded (search-coil technique) in squirrel monkeys while fixation distance (assessed by vergence) was varied using brief presentations of earth-fixed targets at various distances. Stimuli consisted of rotations around an earth-vertical axis and therefore always activated the AVOR. Horizontal and vertical AVORs were assessed when the head was centered over the axis of rotation and oriented upright (UP) and right-side-down (RD), respectively. AVOR gains increased slightly with increasing vergence in darkness, as expected given the small anterior position of the eyes in the head. Combined AVOR/LVOR responses were recorded when subjects were displaced eccentrically from the rotation axis. Eccentric rotations activated the AVOR just as when the head was centered, but added a translational stimulus which generated an LVOR component in response to interaural (IA) or dorsoventral (DV) tangential accelerations, depending on whether the head was UP or RD, respectively. When the head was eccentric and facing nose-out, the AVOR and LVOR produced ocular responses in the same plane and direction (coplanar and synergistic), and response magnitudes increased with increasing vergence. With the head facing nose-in, AVOR and LVOR response components were oppositely directed (coplanar and antagonistic). The AVOR dominated the response when fixation distance was far, and phase was compensatory for head rotation. As fixation distance decreased toward the rotation axis, responses declined to near zero, and when fixation distance approached even closer, the LVOR component dominated and response phase inverted. The same pattern was observed for both horizontal (head UP) and vertical (head RD) responses. The LVOR was recorded directly by rotating subjects eccentrically but in the nose-up (NU) orientation. The AVOR then generated torsional responses to head roll, coexistent with either horizontal or vertical LVOR responses to tangential acceleration when the subject was oriented head-out or right-side-out, respectively. Only the LVOR response components were modulated by vergence. A vectorial analysis of AVOR, LVOR, and combined responses supports the conclusion that AVOR and LVOR response components combine linearly during complex head motion. Received: 27 February 1997 / Accepted: 18 June 1997     

Vestibuloocular reflex of the adult flatfish. III. A species-specific reciprocal pattern of excitation and inhibition

In juvenile flatfish the vestibuloocular reflex (VOR) circuitry that underlies compensatory eye movements adapts to a 90 degrees relative displacement of vestibular and oculomotor reference frames during metamorphosis. VOR pathways are rearranged to allow horizontal canal-activated second-order vestibular neurons in adult flatfish to control extraocular motoneurons innervating vertical eye muscles. This study describes the anatomy and physiology of identified flatfish-specific excitatory and inhibitory vestibular pathways. In antidromically identified oculomotor and trochlear motoneurons, excitatory postsynaptic potentials (EPSPs) were elicited after electrical stimulation of the horizontal canal nerve expected to provide excitatory input. Electrotonic depolarizations (0.8-0.9 ms) preceded small amplitude (<0.5 mV) chemical EPSPs at 1.2-1.6 ms with much larger EPSPs (>1 mV) recorded around 2.5 ms. Stimulation of the opposite horizontal canal nerve produced inhibitory postsynaptic potentials (IPSPs) at a disynaptic latency of 1.6-1.8 ms that were depolarizing at membrane resting potentials around -60 mV. Injection of chloride ions increased IPSP amplitude, and current-clamp analysis showed the IPSP equilibrium potential to be near the membrane resting potential. Repeated electrical stimulation of either the excitatory or inhibitory horizontal canal vestibular nerve greatly increased the amplitude of the respective synaptic responses. These observations suggest that the large terminal arborizations of each VOR neuron imposes an electrotonic load requiring multiple action potentials to maximize synaptic efficacy. GABA antibodies labeled axons in the medial longitudinal fasciculus (MLF) some of which were hypothesized to originate from horizontal canal-activated inhibitory vestibular neurons. GABAergic terminal arborizations were distributed largely on the somata and proximal dendrites of oculomotor and trochlear motoneurons. These findings suggest that the species-specific horizontal canal inhibitory pathway exhibits similar electrophysiological and synaptic transmitter profiles as the anterior and posterior canal inhibitory projections to oculomotor and trochlear motoneurons. Electron microscopy showed axosomatic and axodendritic synaptic endings containing spheroidal synaptic vesicles to establish chemical excitatory synaptic contacts characterized by asymmetrical pre/postsynaptic membrane specializations as well as gap junctional contacts consistent with electrotonic coupling. Another type of axosomatic synaptic ending contained pleiomorphic synaptic vesicles forming chemical, presumed inhibitory, synaptic contacts on motoneurons that never included gap junctions. Altogether these data provide electrophysiological, immunohistochemical, and ultrastructural evidence for reciprocal excitatory/inhibitory organization of the novel vestibulooculomotor projections in adult flatfish. The appearance of unique second-order vestibular neurons linking the horizontal canal to vertical oculomotor neurons suggests that reciprocal excitation and inhibition are a fundamental, developmentally linked trait of compensatory eye movement circuits in vertebrates.     

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.     

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     

Neural circuits underlying tongue movements for the prey-catching behavior in frog: distribution of primary afferent terminals on motoneurons supplying the tongue

The hypoglossal motor nucleus is one of the efferent components of the neural network underlying the tongue prehension behavior of Ranid frogs. Although the appropriate pattern of the motor activity is determined by motor pattern generators, sensory inputs can modify the ongoing motor execution. Combination of fluorescent tracers were applied to investigate whether there are direct contacts between the afferent fibers of the trigeminal, facial, vestibular, glossopharyngeal-vagal, hypoglossal, second cervical spinal nerves and the hypoglossal motoneurons. Using confocal laser scanning microscope, we detected different number of close contacts from various sensory fibers, which were distributed unequally between the motoneurons innervating the protractor, retractor and inner muscles of the tongue. Based on the highest number of contacts and their closest location to the perikaryon, the glossopharyngeal–vagal nerves can exert the strongest effect on hypoglossal motoneurons and in agreement with earlier physiological results, they influence the protraction of the tongue. The second largest number of close appositions was provided by the hypoglossal and second cervical spinal afferents and they were located mostly on the proximal and middle parts of the dendrites of retractor motoneurons. Due to their small number and distal location, the trigeminal and vestibular terminals seem to have minor effects on direct activation of the hypoglossal motoneurons. We concluded that direct contacts between primary afferent terminals and hypoglossal motoneurons provide one of the possible morphological substrates of very quick feedback and feedforward modulation of the motor program during various stages of prey-catching behavior.     

Second-order vestibular neurons form separate populations with different membrane and discharge properties

Membrane and discharge properties were determined in second-order vestibular neurons (2 degrees VN) in the isolated brain of grass frogs. 2 degrees VN were identified by monosynaptic excitatory postsynaptic potentials after separate electrical stimulation of the utricular nerve, the lagenar nerve, or individual semicircular canal nerves. 2 degrees VN were classified as vestibulo-ocular or -spinal neurons by the presence of antidromic spikes evoked by electrical stimulation of the spinal cord or the oculomotor nuclei. Differences in passive membrane properties, spike shape, and discharge pattern in response to current steps and ramp-like currents allowed a differentiation of frog 2 degrees VN into two separate, nonoverlapping types of vestibular neurons. A larger subgroup of 2 degrees VN (78%) was characterized by brief, high-frequency bursts of up to five spikes and the absence of a subsequent continuous discharge in response to positive current steps. In contrast, the smaller subgroup of 2 degrees VN (22%) exhibited a continuous discharge with moderate adaptation in response to positive current steps. The differences in the evoked spike discharge pattern were paralleled by differences in passive membrane properties and spike shapes. Despite these differences in membrane properties, both types, i.e., phasic and tonic 2 degrees VN, occupied similar anatomical locations and displayed similar afferent and efferent connectivities. Differences in response dynamics of the two types of 2 degrees VN match those of their pre- and postsynaptic neurons. The existence of distinct populations of 2 degrees VN that differ in response dynamics but not in the spatial organization of their afferent inputs and efferent connectivity to motor targets suggests that frog 2 degrees VN form one part of parallel vestibulomotor pathways.     

Brain stem pursuit pathways: dissociating visual,vestibular, and proprioceptive inputs during combined eye-head gaze tracking

Eye-head (EH) neurons within the medial vestibular nuclei are thought to be the primary input to the extraocular motoneurons during smooth pursuit: they receive direct projections from the cerebellar flocculus/ventral paraflocculus, and in turn, project to the abducens motor nucleus. Here, we recorded from EH neurons during head-restrained smooth pursuit and head-unrestrained combined eye-head pursuit (gaze pursuit). During head-restrained smooth pursuit of sinusoidal and step-ramp target motion, each neuron's response was well described by a simple model that included resting discharge (bias), eye position, and velocity terms. Moreover, eye acceleration, as well as eye position, velocity, and acceleration error (error = target movement - eye movement) signals played no role in shaping neuronal discharges. During head-unrestrained gaze pursuit, EH neuron responses reflected the summation of their head-movement sensitivity during passive whole-body rotation in the dark and gaze-movement sensitivity during smooth pursuit. Indeed, EH neuron responses were well predicted by their head- and gaze-movement sensitivity during these two paradigms across conditions (e.g., combined eye-head gaze pursuit, smooth pursuit, whole-body rotation in the dark, whole-body rotation while viewing a target moving with the head (i.e., cancellation), and passive rotation of the head-on-body). Thus our results imply that vestibular inputs, but not the activation of neck proprioceptors, influence EH neuron responses during head-on-body movements. This latter proposal was confirmed by demonstrating a complete absence of modulation in the same neurons during passive rotation of the monkey's body beneath its neck. Taken together our results show that during gaze pursuit EH neurons carry vestibular- as well as gaze-related information to extraocular motoneurons. We propose that this vestibular-related modulation is offset by inputs from other premotor inputs, and that the responses of vestibuloocular reflex interneurons (i.e., position-vestibular-pause neurons) are consistent with such a proposal.     

Linearity of canal-otolith interaction during eccentric rotation in humans

During natural behavior, the head may simultaneously undergo rotation, transduced by the semicircular canals, and translation, transduced by the otolith organs. It has been demonstrated in monkey that the vestibulo-ocular reflexes (VORs) elicited by both endorgans (i.e., the angular and linear VORs, or AVOR and LVOR) sum linearly during combined rotation and translation, but this finding has proven more elusive in humans. To investigate the combined AVOR/LVOR response, six human subjects underwent yaw eccentric rotation at 3 Hz in darkness while displaced from the axis of rotation. Responses to on-center yaw rotation (AVOR alone) and interaural translation (LVOR alone) were also recorded. During eccentric rotation with the subject facing away from the axis of rotation (i.e., nose out), in which a yaw to the right occurs simultaneously with a translation to the right (i.e., translation in phase with rotation), the AVOR and LVOR acted synergistically. Responses were always out of phase with rotation, and became larger in magnitude as vergence increased. For nose-in eccentric rotation, during which translation is out of phase with rotation, the LVOR acted antagonistically to the AVOR. During near viewing, the LVOR often dominated the overall response when eccentricity was sufficiently large, producing eye movements that were in phase with the rotational stimuli. As vergence decreased, the LVOR influence diminished, eventually resulting in responses that were out of phase with rotation at lowest vergence. When the response to pure yaw rotation was vectorially removed from the responses to eccentric rotation, the results proved statistically indistinguishable from the LVOR recorded during interaural translation, suggesting that the ocular response to combined angular and linear motion reflects the linear combination of the AVOR and LVOR.     

Lesion-induced vestibular plasticity in the frog: are N-methyl-D-aspartate receptors involved?

Summary The synaptic excitation of central vestibular neurons in the isolated superfused brainstem of chronic hemilabyrinthectomized (HL) frogs and of controls was studied electrophysiologically and pharmacologically. Central vestibular neurons were excited either through vestibular afferent fibers or through the vestibular commissural pathway by means of electrical stimulation of the ipsilateral or the contralateral VIIIth nerve. In chronic HL frogs, commissural field potential amplitudes were on the average larger than those of intact frogs and the shape parameters of intracellularly recorded commissural EPSPs of chronic animals were on the average shifted towards those of vestibular afferent EPSPs. In control frogs, vestibular afferent EPSPs were generated independently from N-methyl-D-aspartate (NMDA) receptors, whereas commissural EPSPs exhibited a delayed NMDA receptor mediated component. Commissural EPSPs of HL frogs exhibited a NMDA receptor mediated component as well. The size of this EPSP component was larger when the time to peak of the EPSP was longer. EPSPs with similar rise times exhibited NMDA mediated components of similar size, irrespective of whether they originated from chronic animals or controls. The tendency of these EPSPs towards shorter rise times in chronic animals was paralled by a similar decrease of the relative size of their NMDA receptor mediated component. It is concluded that the increased synaptic efficacy of commissural fibers observed in chronic HL frogs does not result from an increased NMDA receptor component.     

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.     

Characterization and adaptive modification of the goldfish vestibuloocular reflex by sinusoidal and velocity step vestibular stimulation.

1. The normal and adapted vestibuloocular reflex (VOR) of goldfish was characterized by means of sinusoidal, velocity step, and position step head rotations about the vertical axis. VOR adaptation was induced by short-term, 1- to 4-h, presentation of visual and vestibular stimuli that altered the ratio of eye to head velocity. 2. The VOR response measured with sinusoidal oscillations in the dark was close to ideal compensatory values over 2 decades (1/32-2 Hz). Gain approximated unity, and phase, in relation to the head, was nearly 180 degrees. The VOR was linear within the range of head velocity tested (4-64 degrees/s). 3. Head velocity steps from 1/8 to 1 Hz produced steplike eye velocity profiles that could be divided into an early acceleration-related "dynamic" component and a later constant-velocity "sustained" period frequently separated by a sag at approximately 0.1-0.15 s from the initiation of eye movement. The sustained response exhibited no decay during the constant-velocity component of the step. 4. Higher temporal resolution of the dynamic response showed the adducting eye movement to have a shorter latency, faster rise time, and larger peak gain than the abducting eye movement. The characteristics of this directional asymmetry were similar for position steps and electrical stimulation of the vestibular nerve. However, the asymmetry was not observed during sinusoidal head rotation, the sustained component of the step response, or after electrical stimulation of the VIth and IIIrd nerves. We conclude that this directional asymmetry is of central origin and may be largely due to the parallel vestibular and abducens internuclear neuron pathways onto medial rectus motoneurons. 5. The VOR adaptation process for both higher and lower eye velocity exhibited an exponential time course with time constants of 55 and 45 min, respectively. After continuous sinusoidal training for 4 h, VOR gain reached an asymptotic level 5% away from perfect suppression in the low-gain training, but 19% away from the actual performance in the high-gain paradigm. The time constant for VOR gain reversal was 5 h, and an asymptotic level 40% less than performance was reached within 10 h. 6. Adapted VOR gain was symmetrical for both directions of eye movement measured either during sinusoidal rotation or the sustained part of the velocity step. VOR adaptation also produced a comparable gain change in the nasal and temporal directions of the dynamic component, but this reflected the asymmetric characteristics observed in the preadapted condition.(ABSTRACT TRUNCATED AT 400 WORDS)     

Afferent diversity and the organization of central vestibular pathways

This review considers whether the vestibular system includes separate populations of sensory axons innervating individual organs and giving rise to distinct central pathways. There is a variability in the discharge properties of afferents supplying each organ. Discharge regularity provides a marker for this diversity since fibers which differ in this way also differ in many other properties. Postspike recovery of excitability determines the discharge regularity of an afferent and its sensitivity to depolarizing inputs. Sensitivity is small in regularly discharging afferents and large in irregularly discharging afferents. The enhanced sensitivity of irregular fibers explains their larger responses to sensory inputs, to efferent activation, and to externally applied galvanic currents, but not their distinctive response dynamics. Morphophysiological studies show that regular and irregular afferents innervate overlapping regions of the vestibular nuclei. Intracellular recordings of EPSPs reveal that some secondary vestibular neurons receive a restricted input from regular or irregular afferents, but that most such neurons receive a mixed input from both kinds of afferents. Anodal currents delivered to the labyrinth can result in a selective and reversible silencing of irregular afferents. Such a functional ablation can provide estimates of the relative contributions of regular and irregular inputs to a central neuron’s discharge. From such estimates it is concluded that secondary neurons need not resemble their afferent inputs in discharge regularity or response dynamics. Several suggestions are made as to the potentially distinctive contributions made by regular and irregular afferents: (1) Reflecting their response dynamics, regular and irregular afferents could compensate for differences in the dynamic loads of various reflexes or of individual reflexes in different parts of their frequency range; (2) The gating of irregular inputs to secondary VOR neurons could modify the operation of reflexes under varying behavioral circumstances; (3) Two-dimensional sensitivity can arise from the convergence onto secondary neurons of otolith inputs differing in their directional properties and response dynamics; (4) Calyx afferents have relatively low gains when compared with irregular dimorphic afferents. This could serve to expand the stimulus range over which the response of calyx afferents remains linear, while at the same time preserving the other features peculiar to irregular afferents. Among those features are phasic response dynamics and large responses to efferent activation; (5) Because of the convergence of several afferents onto each secondary neuron, information transmission to the latter depends on the gain of individual afferents, but not on their discharge regularity. Received: 22 March 1999 / Accepted: 21 July 1999