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The influence of middle ear pressure on the otolith system in cats.

The influence of varying middle ear pressure on the otolith system was investigated in anesthetized cats. Extra-axonal recordings of action potentials were performed in the vestibular nerve fibers and in the neurons in the lateral vestibular nucleus that responded to lateral or anteroposterior steady-state tilt. Positive or negative pressure was applied to the ipsilateral middle ear during the recordings. Seventy-three percent of the fibers and 63% of the neurons responded to changes in the middle ear pressure. These response rates were higher than those previously reported on the units innervating semicircular canals. Findings suggest that the otolith organs are more sensitive to changes in the middle ear pressure than are the semicircular canals. The units responding to lateral tilt were more sensitive to middle ear pressure than those that responded to anteroposterior tilt. Displacement of endolymph caused by pressure changes in the middle ear was considered to have affected the activities of hair cells in otolith organs.

Animals↗

Projections of the individual vestibular end-organs in the brain stem of the squirrel monkey.

The central nervous system (CNS) projections of primary afferent neurons from individual vestibular receptors were studied using horseradish peroxidase (HRP) or biocytin labeling in 14 ears from 7 adult squirrel monkeys using the technique developed in the chinchilla (Lee et al., 1989, 1992). The specificity of labeling was verified by examining the location of the labeled fibers and cell bodies in the vestibular nerve and Scarpa's ganglion. Labeled fibers and cells were restricted to nerves and areas belonging to groups of cells in either the superior or the inferior ganglion of the vestibular nerve. In the vestibular nerve root, labeled primary afferent fibers also exhibited a receptor-dependent segregation at the entrance to the medulla. Fibers from the HSC and the SSC were found rostrally and those from the PSC and the SAC were found in the caudal area. The UTR fibers were situated intermediate between these two groups of fibers. (A bundle of fibers, probably vestibular efferents, was identified immediately rostrally and ventromedially to the UTR fibers.) The primary afferent fibers bifurcated into secondary ascending and descending fibers at the lateral border of the vestibular nuclei, forming a longitudinal rostrocaudal vestibular tract. The secondary fibers from individual end-organs occupied specific locations in the tract: the UTR fibers were dorsal to the SSC and the HSC fibers, PSC fibers were found most medially, and the SAC fibers occupied the lateralmost area. The secondary UTR fibers overlapped considerably with those of the SSC and the HSC. The orderly receptor-dependent segregation of fibers was more prominent in the descending tracts than in the ascending tracts. In the vestibular nuclei complex the location of the tertiary branches of various end-organs exhibited considerable overlap within the major vestibular nuclei (SN, superior nucleus; LN, lateral nucleus; MN, medial nucleus; DN, descending nucleus). There were still differences, however, in the projection pattern. Fibers from the SAC ran primarily in the lateral area, fibers from the SSC and the UTR were found ventromedially to the SAC fibers, and the HSC projected slightly medially to the fibers from the SSC. The PSC fibers projected most medially. The UTR and SAC sent numerous fibers to the cerebellum. Fibers from the semicircular canals projected through the rostrodorsal region of the SN and presumably also projected to the cerebellum. The precise termination of fibers was evaluated by studying the location of labeled boutons, which were identified in all major vestibular nuclei. Labeled boutons from all the receptors were in the rostral and central areas of the SN, and in the MN mainly in the rostral two-thirds. In the LN, boutons from all the receptors were in the rostroventral part, most of which were from the UTR and SAC. No labeled boutons were in the caudodorsal part of this nucleus. Labeled boutons in the DN primarily surrounded the descending tract fibers and were particularly prominent medially. In specimens in which superior vestibular nerve receptor organs were scratched vestibular efferent fibers were also labeled. These fibers traveled in the most ventral part of the vestibular nerve root and projected in the ventral aspect of the LN to labeled soma in the ipsilateral and contralateral brain stem. Specificity the in projection patterns of efferent fibers from different end-organs could not be ascertained.

Animals↗

Primary vestibular projections in the chinchilla.

The central projections of fibers from the vestibular nerve were studied in 19 chinchillas after horseradish peroxidase labelling. In addition, the limits of the vestibular nuclei and the anatomical characteristics of their neurons were also studied. All five vestibular nuclei received primary afferents, but there were extensive areas of them that received very little or no projections at all, such as the rostral part of the superior vestibular nucleus, the dorsocaudal part of the lateral vestibular nucleus, the caudal half of the medial vestibular nucleus and the caudalmost aspect of the dorsal vestibular nucleus.

Afferent Pathways↗

Neural network models of velocity storage in the horizontal vestibulo-ocular reflex.

The vestibulo-ocular reflex (VOR) produces compensatory eye movements by utilizing head rotational velocity signals from the semicircular canals to control contractions of the extraocular muscles. In mammals, the time course of horizontal VOR is longer than that of the canal signals driving it, revealing the presence of a central integrator known as velocity storage. Although the neurons mediating VOR have been described neurophysiologically, their properties, and the mechanism of velocity storage itself, remain unexplained. Recent models of integration in VOR are based on systems of linear elements, interconnected in arbitrary ways. The present study extends this work by modeling horizontal VOR as a learning network composed of nonlinear model neurons. Network architectures are based on the VOR arc (canal afferents, vestibular nucleus (VN) neurons and extraocular motoneurons) and have both forward and lateral connections. The networks learn to produce velocity storage integration by forming lateral (commissural) inhibitory feedback loops between VN neurons. These loops overlap and interact in a complex way, forming both fast and slow VN pathways. The networks exhibit some of the nonlinear properties of the actual VOR, such as dependency of decay rate and phase lag upon input magnitude, and skewing of the response to higher magnitude sinusoidal inputs. Model VN neurons resemble their real counterparts. Both have increased time constant and gain, and decreased spontaneous rate as compared to canal afferents. Also, both model and real VN neurons exhibit rectification and skew. The results suggest that lateral inhibitory interactions produce velocity storage and also determine the properties of neurons mediating VOR. The neural network models demonstrate how commissural inhibition may be organized along the VOR pathway.

Eye Movements↗

Vestibular mechanisms involved in idiopathic scoliosis.

Patients affected by idiopathic scoliosis (IS) show not only a spinal deformity, but also postural and oculomotor deficits suggesting that such syndrome can be related to a vestibular disfunction. It appears, however, that, in children, a slight unbalance in the activity of vestibular complex of both sides escapes the neuronal mechanisms responsible for vestibular compensation and leads to the spinal curvature which characterises IS. Such process could be reinforced by a disrupted integration of vestibular and visual signals at cortical level, leading to an altered perception of the vertical and to abnormal motor commands. In addition to the classical ascending and descending pathways arising from the vestibular nuclei, which utilize glutamate or GABA as neurotransmitters, labyrinthine afferents may also affect spinal, cerebellar and cerebrocortical structures, through the noradrenergic and serotoninergic systems, which originate from the locus coeruleus and the raphe nuclei, respectively. Due to the role of these neuromodulators in brain plasticity, a disruption in the activity of monoaminergic neurons could favour the development of postural and oculomotor deficits. An impaired release of monoamine at cerebrocortical level could also explain the cognitive deficits which may occur in IS patients.

Biogenic Monoamines↗

Firing behavior of brain stem neurons during voluntary cancellation of the horizontal vestibuloocular reflex. II. Eye movement related neurons.

1. The single-unit activity of neurons in the vestibular nucleus, the prepositus nucleus, and the abducens nucleus, whose activity was primarily related to horizontal eye movements, was recorded in alert squirrel monkeys that were trained to track a small visual target by generating smooth pursuit eye movements and to cancel their horizontal vestibuloocular reflex (VOR) by fixating a head stationary target. 2. The spiking behavior of each cell was recorded during 1) spontaneous eye movements, 2) horizontal smooth pursuit of a target that was moved sinusoidally +/- 20 degrees/s at 0.5 Hz, 3) horizontal VOR evoked by 0.5-Hz sinusoidal turntable rotations +/- 40 degrees/s (VORs), and 4) voluntary cancellation of the VOR by fixation of a head-stationary target during 0.5-Hz sinusoidal turntable rotation at +/- 40 degrees/s (VORCs). The responses of most (28/42) of the units were recorded during unpredictable 100-ms steps in head acceleration (400 degrees/s2) that were generated while the monkey was fixating a target light. The acceleration steps were generated either when the monkey was stationary or when the turntable was already rotating (VORt trials), and the monkey was canceling its VOR (VORCt trials). 3. The firing behavior of all 12 of the abducens neurons recorded was closely related to horizontal eye position and eye velocity during all of the behavioral paradigms used, although there was a small but significant increase in the eye position sensitivity of many of these units when the eye was moving (smooth pursuit) versus when the eye was stationary (fixation). 4. Many neurons in the prepositus nucleus and the medial vestibular nucleus (n = 15) were similar to abducens neurons, in that their firing rate was related primarily to horizontal eye position and eye velocity, regardless of the behavioral paradigm used. These cells were, on average, more sensitive to eye position and smooth pursuit eye velocity than were abducens neurons. 5. The firing rate of 15 other neurons in the prepositus and medial vestibular nucleus was related primarily to horizontal smooth pursuit eye movements. The tonic firing rate of all of these smooth pursuit (SP) cells was related to horizontal eye position, and the majority generated bursts of spikes during saccades in all directions but their off direction. Six of the SP neurons fired in phase with ipsilateral eye movements, whereas the remaining nine were sensitive to eye movements in the opposite direction.(ABSTRACT TRUNCATED AT 400 WORDS)

Abducens Nerve↗

Contributions of placodal and neural crest cells to avian cranial peripheral ganglia.

The method of embryonic tissue transplantation was used to confirm the dual origin of avian cranial sensory ganglia, to map precise locations of the anlagen of these sensory neurons, and to identify placodal and neural crest-derived neurons within ganglia. Segments of neural crest or strips of presumptive placodal ectoderm were excised from chick embryos and replaced with homologous tissues from quail embryos, whose cells contain a heterochromatin marker. Placode-derived neurons associated with cranial nerves V, VII, IX, and X are located distal to crest-derived neurons. The generally larger, embryonic placodal neurons are found in the distal portions of both lobes of the trigeminal ganglion, and in the geniculate, petrosal and nodose ganglia. Crest-derived neurons are found in the proximal trigeminal ganglion and in the combined proximal ganglion of cranial nerves IX and X. Neurons in the vestibular and acoustic ganglia of cranial nerve VIII derive from placodal ectoderm with the exception of a few neural crest-derived neurons localized to regions within the vestibular ganglion. Schwann sheath cells and satellite cells associated with all these ganglia originate from neural crest. The ganglionic anlagen are arranged in cranial to caudal sequence from the level of the mesencephalon through the third somite. Presumptive placodal ectoderm for the VIIIth, the Vth, and the VIIth, IXth, and Xth ganglia are located in a medial to lateral fashion during early stages of development reflecting, respectively, the dorsolateral, intermediate, and epibranchial positions of these neurogenic placodes.

Animals↗

Neuronal coding of linear motion in the vestibular nuclei of the alert cat. I. Response characteristics to vertical otolith stimulation.

The aim of the present study was to investigate some aspects of the central processing of otolith information during linear motion. For this purpose, the response characteristics of 69 vestibular nuclei units to sinusoidal otolith stimulation in the vertical Z axis were analysed in the alert cat. Among this population of neurons which responded to a 0.05 Hz, 290 mm translation, 47 units (70%) displayed a firing rate modulation which followed the input frequency (H1 units). The majority of these neurons exhibited an increase in discharge rate during upward displacement, with a response phase close to the motion velocity or slightly leading downward acceleration. The acceleration related units were divided into two groups according to whether they showed clear increases or only a slight change in discharge rate when the stimulus frequency was increased. The former group was characterized by an average -16.3 dB drop in gain (from 43.9 +/- 1.8 dB, S.D. to 27.6 +/- 7 dB, S.D.) within the 0.05 Hz-0.5 Hz frequency range, while the latter group displayed an average -31.2 dB gain attenuation (from 45.1 +/- 1.1 dB, S.D. to 13.9 +/- 0 dB) within the same decade. In contrast to differences in response gain, all the units tested exhibited a relatively stable phase lead of about 20 degrees with respect to downward peak acceleration. Conversely, units whose response was close to motion velocity in the lower frequency range (0.05 Hz-0.10 Hz) displayed a strong phase lead of about 100 degrees when the stimulus frequency was increased (up to 0.50 Hz). These neurons were thus characterized by an acceleration related response in the higher frequency range. At the same time, an average -24.8 dB gain attenuation (from 47.7 +/- 3.4 dB to 22.9 +/- 3.7 dB) was found in the 0.05 Hz-0.5 Hz decade. The remaining 22 neurons (30%) were called H2 units since they displayed a response waveform double that of the input frequency, a response already described during sinusoidal rotation. Unit discharge reached a peak approximately in phase with maximum upward and downward velocity. Asymmetrical change in unit firing rate about the resting discharge level and different dynamic behavior of the upward and downward response components were usually found. These response characteristics suggest that the H2 patterns are centrally constructed and could result from convergence of otolith afferents having opposite polarization vectors.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Second-order vestibular adaptation and cupular dynamics.

The magnitude of initial response and slope of continued response of 45 neurons in the vestibular nuclei of cats to constant and interrupted accelerations were investigated. Eighty-eight percent exhibited adaptation, the magnitude of which was proportional to the stimulus. Comparison of slope and intercept of the response to continuous acceleration before and after a superimposed inhibitory velocity change suggests that the adaptation phenomenon is unrelated to cupular position.

Acceleration↗

[Distribution of vestibular nerve fiber endings in the ventral vestibular nucleus of the stato-acoustic complex of the medulla oblongata in Rana temporaria frogs].

Electronmicroscopic studies have been made on the distribution of the primary vestibular afferents after sectioning the VIIIth nerve in the frog Rana temporaria. The projections of the vestibular nerve fibers extend ipsilaterally. Some of the primary vestibular afferents are connected with the second-order neurons by means of electrotonic contacts. Degeneration of postsynaptic components was found in axo-axonal synapses. Some of the vestibular neurons send axons to the labyrinth. Possible functional significance of these findings is discussed.

Animals↗

Ultrastructural evidence of repair and neuronal survival after labyrinthectomy in the squirrel monkey.

Although the vestibular and cochlear branches of the VIIIth cranial nerve originate embryologically from the same primordia, results of the present investigation confirm previous findings indicating that the vestibular branch may be more plastic with respect to recovery after surgical insult than the cochlear division. In this report we show ultrastructural details of changes undergone by the vestibular nerve after surgery. Dendrites peripheral to the vestibular nerve ganglion (VNG) were severed by surgically removing the vestibular end organs; the squirrel monkeys were then allowed to recuperate, and tested for their vestibulospinal and vestibulo-oculomotor functions behaviorally. However, behavior deficits resulting from the injury are reported separately. The vestibular nerves excised from the internal acoustic meatus and the temporal bones were examined histologically for changes of VNG and fibers from day 1 to 1,247 days after labyrinthectomy. Light- and electron-microscopic examinations indicated that some perikarya and some fibers of the VNG remained in the ganglionic matrix for up to 1,247 days, the longest period studied, after the operation. Fibers extended toward the remodeled inner ear space in the absence of appropriate sensory cell targets. The surviving neurons and fibers exhibited various degrees of wallerian-like degeneration at first, but many of them retained ultracellular organelles and integrity even after 1,247 days. Since vestibular perikarya are bipolar, the unsevered fibers that project to the brainstem could retain functional synaptic connections, a possibility that is now under investigation. Schwann cells in the ganglionic matrix may also have contributed to vestibular neuron survival by providing the proper nourishment. Morphometric measurements determined that neurons remaining in the ganglion had significantly smaller cross-sectional areas than normal neurons.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Partial restitution of lesion-induced deficits in the horizontal vestibulo-ocular reflex performance measured from the bilateral abducens motor output in frogs.

The responses of the bilateral abducens nerves to small table velocity steps in the dark were measured in four groups of animals: One group was intact prior to recording (controls), one group was hemi-labyrinthectomized the day before the recordings (acute HL), the horizontal canal nerve was sectioned the day before the recordings (acute HCN) in another and the last group was hemi-labyrinthectomized between 60 and 90 days prior to recording (chronic HL). In controls (N = 6) the slopes of the change in discharge rate to increasingly larger velocity steps increased maximally with about 200 imp/s per 1 degree/s and decreased maximally with about -60 imp/s per 1 degree/s. This difference is explained by low resting rates and by recruitment of spontaneously inactive vestibular afferent, central vestibular and abducens neurons. Results obtained from acute HL (N = 4) and acute HCN (N = 4) animals were practically identical. In neither case was a spontaneous nystagmic activity pattern observed. Results differed from those obtained in controls due to an asymmetric reduction in responsiveness. Comparison of the slopes of the evoked increases and decreases in discharge rates of abducens nerves to increasingly larger velocity steps with those in controls show that normal abducens responses are predominantly controlled by crossed excitation and by uncrossed inhibition. Disinhibition and disfacilitation play minor roles. In chronic HL animals (N = 6) that had posturally recovered to a similar degree, responses evoked by steps towards the intact side at larger velocity steps were slightly reduced with respect to those in acute HL or HCN animals. Responses evoked by steps towards the lesioned side differed between individuals. They were either similar to those in controls (N = 1), to those in acute animals (N = 2) or lay between these two extremes (N = 3). The improvement in response to velocity steps towards the lesioned side in 4 of 6 animals is explained by an increase in activity released by disinhibition. This inhibition in turn is controlled by horizontal canal-dependent input from the intact side. Plugging of this canal abolished all direction-specific responses in this plane in the dark, suggesting that the partial restitution of function of horizontal reflex performance depends exclusively on signals derived from receptors of this canal.

Abducens Nerve↗

Recent advances in the pharmacology of the vestibulo-ocular reflex system.

Recent advances in the pharmacology of the vestibulo-ocular reflex have had a major impact on our understanding of the vestibular system, the sensory system primarily concerned with the stabilization of gaze and posture during head movement. Increasing evidence suggests that afferent transmission from the receptor hair cells in the vestibular labyrinth to the vestibular nerve probably involves glutamate acting on a number of excitatory amino acid receptor subtypes. Furthermore, hair-cell sensitivity appears to be regulated by cholinergic, GABA-mediated and, possibly, peptide-mediated efferent feedback from the CNS. Likewise, it seems clear that an excitatory amino acid, probably glutamate, is the major transmitter used by the vestibular nerve in its synapses with neurones of the brainstem vestibular nucleus. In this review, Paul Smith and Cynthia Darlington discuss the large number of receptor subtypes that have been identified in the vestibular nucleus, including receptors for several peptides that may have a role in co-transmission.

Animals↗

The synaptic activation of N-methyl-D-aspartate receptors in the rat medial vestibular nucleus.

1. We examined the synaptic activation of N-methyl-D-aspartate (NMDA) receptors by stimulation of primary vestibular afferent projections to second-order neurons in the medial vestibular nucleus (MVN) using whole cell patch-clamp recording methods in rat brain stem slices maintained in vitro. 2. Stimulation of the vestibular nerve (nVIII) evoked monosynaptic excitatory postsynaptic potentials (EPSPs) in second-order MVN neurons. Bath application of the gamma-aminobutyric acid receptor antagonist bicuculline (10 microM) revealed a late, slow EPSP that was blocked by the NMDA receptor antagonist D-2-amino-5-phosphonovalerate (D-AP5; 50 microM) and displayed a voltage-dependent reduction at hyperpolarized potentials in the presence of external magnesium (1 mM). The early component of the nVIII-evoked EPSP in the presence of bicuculline was blocked by the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor antagonist 6,7-dinitroquinoxaline-2,3-dione (DNQX; 10 microM) and displayed linear current-voltage relations in the presence of external magnesium. 3. In some cells both components of the EPSP were blocked by DNQX, whereas only the late component was sensitive to D-AP5, indicating that NMDA receptors also mediate excitation via intrinsic pathways within MVN. 4. The NMDA receptor-mediated excitatory postsynaptic current (EPSC) evoked by nVIII stimulation was recorded in voltage-clamped MVN neurons in a magnesium-free saline containing bicuculline (10 microM) and DNQX (10 microM). At -80 mV the NMDA receptor-mediated EPSC (latency = 2.7 ms) displayed a slow rise time (10-90%, 5.8 ms) and exhibited a biexponential decay [time constant of fast component of decay (tau s) = 27.6 ms, time constant of slow component of decay (tau s) = 147.4 ms].(ABSTRACT TRUNCATED AT 250 WORDS)

Afferent Pathways↗