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Conflicting visual-vestibular stimulation and vestibular nucleus activity in alert monkeys.

In alert Rhesus monkeys (Macaca mulatta) neuronal activity of vestibular nuclei was recorded during pure vestibular and conflicting visual-vestibular stimulation. Pure vestibular stimulation consisted of rotating the monkey about the vertical axis in complete darkness. During conflicting visual-vestibular stimulation the monkeys were rotated in the light within a vertically striped cylinder mechanically coupled to the turntable. The conflict is that although the monkey is accelerated, there is no relative movement between visual surrounding and the animal. In the conflict situation thresholds of neuronal modulation and of nystagmus were raised compared with those during pure vestibular stimulation. Nystagmus slow-phase velocity could always be dissociated from the neuronal activity, the nystagmus often being totally suppressed whereas the neuronal activity was only attenuated. This suggests a further information processing between vestibular and oculomotor nuclei in the generation of nystagmus.

Animals↗

Limb input to the cat vestibular nuclei.

The input from fore- and hindlimbs to the vestibular nuclear complex (VNC) was investigated in awake cats. Electrical stimulus was given to the sciatic, radial and vestibular nerves bilaterally and single unit responses were recorded in the VNC with extracellular technique. The position of the microelectrode was histologically confirmed. All four major vestibular nuclei received fore- as well as hindlimb input. Forty per cent of the neurons with limb input also received vestibular afferents. No major distinguishing features appeared between the different nuclei with regard to response characteristics. Certain differences in laterality of response, quantitative fore-hindlimb ratio and somatosensory-labyrinthine convergence were observed however. Response latencies to sciatic and radial nerve stimuli always exceeded a 3 msec and were grouped around 8 and 16 msec. A third population of vestibular neurons had latencies over 20 msec. Both excitatory and inhibitory responses were recorded, with the latter not always following an activation. The findings illustrate the complex nature of the ascending pathway to the VNC and the integrative properties of this complex.

Action Potentials↗

Gamma amino butyric acid (GABA) immunoreactivity in the vestibular nuclei of normal and unilateral vestibular neurectomized cats.

Recent neurochemical investigations of the central vestibular pathways have demonstrated that several neurotransmitters are involved in various operations required for stabilizing posture and gaze. Neurons of the vestibular nuclei (VN) receive GABAergic inhibitory afferents, and GABAergic neurons distributed throughout the vestibular complex are implicated in inhibitory vestibulo-ocular and vestibulo-spinal pathways. The aim of this study was to analyse the modifications of GABA immunoreactivity (GABA-ir) in the cat VN after unilateral vestibular neurectomy (UVN). Indeed, compensation of vestibular deficits is a good model for studying adult central nervous system (CNS) plasticity and the GABAergic system is involved in CNS plasticity. We studied GABA-ir by using a purified polyclonal antibody raised against GABA. Light microscopic preparations of thin (20 microm) sections of cat VN were used to quantify GABA-ir by an image analysing system measuring GABA-positive punctate structures and the number of GABA-positive neurons. Both the lesioned and intact sides were analysed in three populations of UVN cats killed at different times after injury (1 week, 3 weeks and 1 year). These data were compared to those collected in normal unlesioned and sham-operated cats. Results showed a spatial distribution of GABA-ir in the control cats that confirmed previous studies. GABA-ir neurons, fibres and nerve terminals were scattered in all parts of the VN. A higher concentration of GABA-positive neurons (small cells) was detected in the medial and inferior VN (MVN and IVN) and in the dorsal part of the lateral VN (LVNd). A higher level of GABA-positive punctate structures was observed in the MVN and in the prepositus hypoglossi (PH) nucleus. Lesion-induced changes were found at each survival time. One week after injury the number of GABA-positive neurons was significantly increased in the MVN, the IVN and the dorsal part of the LVN on the lesioned side and in the ventral part of the LVN on the intact side. One year later a bilateral increase in GABA-positive neurons was detected in the MVN whilst a bilateral decrease was observed in both the SVN and the ventral part of the LVN. Changes in the GABA-staining varicosities did not strictly coincide with the distribution of GABA-ir cells, suggesting that GABA-ir fibres and nerve terminals were also modified. One week and later after injury, higher GABA-staining varicosities were seen unilaterally in the ipsilateral MVN. In contrast, bilateral increases (in PH) and bilateral decreases (in SVN and the ventral part of the LVN) were recorded in the nearly (3 weeks) or fully (1 year) compensated cats. At this stage GABA-staining varicosities were significantly increased in the lesioned side of the MVN. These findings demonstrate the reorganization of the GABAergic system in the VN and its possible role in recovery process after UVN in the cat. The changes seen during the acute stage could be causally related to the VN neuron deafferentation, contributing to the static vestibular deficits. Those found in the compensated cats would be more functionally implicated in the dynamic aspects of vestibular compensation.

Adaptation, Physiological↗

Serotonin-evoked modifications of the neuronal firing rate in the superior vestibular nucleus: a microiontophoretic study in the rat.

Microiontophoretic ejection (10-100 nA) of serotonin (5-hydroxytryptamine) into the superior vestibular nucleus induced modifications of the mean firing rate in 87% of the neurons examined. The responses to 5-hydroxytryptamine application were excitatory in 48% of the cells, inhibitory in 29%, and biphasic (inhibitory/excitatory) in the remaining 10%. The excited neurons were scattered throughout the nucleus; the units inhibited or characterized by biphasic responses were distinctly more numerous in the ventrolateral sector of the nucleus. The magnitude of both excitatory and inhibitory effects was dose-dependent. The excitatory responses to 5-hydroxytryptamine were blocked or greatly reduced by two 5-hydroxytryptamine antagonists, methysergide and ketanserin, or even reversed in many cases. Inhibitory responses were enhanced by simultaneous application of 5-hydroxytryptamine antagonists in half of the units studied. In the remaining units, ketanserin left the response unmodified, whereas methysergide reduced but never quite blocked it. The application of 5-methoxy-N,N- dimethyltryptamine, a 5-hydroxytryptamine agonist more effective on 5-hydroxytryptamine1 than on 5-hydroxytryptamine2 receptors, and of 8-hydroxy-2(di-n-propyl-amino) tetralin, a 5-hydroxytryptamine1A-specific agonist, induced a decrease in the firing rate which was unaffected by methysergide. These results support the hypothesis that 5-hydroxytryptamine exerts various functions throughout the superior vestibular nucleus by various receptors and that the inhibitory action is limited to an area of it.(ABSTRACT TRUNCATED AT 250 WORDS)

8-Hydroxy-2-(di-n-propylamino)tetralin↗

Responses of lateral reticular neurons to sinusoidal stimulation of labyrinth receptors in decerebrate cat.

1. The electrical activity of 106 individual neurons located in the precerebellar lateral reticular nucleus (NRL) and the surrounding medullary reticular formation (RF) has been recorded in precollicular decerebrate cats during sinusoidal tilt around the longitudinal axis of the whole animal leading to stimulation of labyrinth receptors. 2. Among these lateral reticular neurons tested, 48 of 712 (67.6%) NRL neurons and 11 of 35 (31.4%) RF neurons responded to slow rotation of the animal at the standard frequency of 0.026 Hz and at the peak amplitude of displacement of 5-10 degrees. 3. All the responsive units showed a periodic modulation of firing rate during the sinusoidal stimulus. In particular, 35 of 57 units (i.e., 61.4%) were excited during side-up and depressed during side-down tilt of the whole animal; on the other hand, 14 of 57 units (i.e., 24.6%) showed the opposite behavior. In both instances, the peak of the responses occurred with an average phase lead of about 16 degrees with respect to the extreme side-up or side-down position of the animal. The remaining eight units (i.e., 14%) showed a phase shift of the peak of their response of about 90 degrees with respect to the animal position. 4. The sensitivity of the responses, expressed in percentage change of the average firing rate per degree of displacement, did not change by increasing the peak amplitude of tilt from 5 to 15 degrees at the frequency of 0.026 Hz. This finding indicates that the system was relatively linear with respect to the amplitude of stimulation. The sensitivity of the units, however, slightly increased but the phase angle of the responses did not change by increasing the frequency of tilting from 0.015 to 0.15 Hz at the peak amplitude of 5 or 10 degrees. These findings indicate that the responses depended on stimulation of macular labyrinth receptors. 5. Most of the lateral reticular units affected by tilt received also a bilateral convergent input from the hindlimbs. 6. These observations are related to the results of previous studies in which the responses of macular afferents, vestibular nuclei neurons, and corticocerebellar Purkinje (P) cells to sinusoidal tilt of the whole animal have been investigated. A possible role of lateral reticular neurons in the labyrinth control of posture in decerebrate cat is also discussed.

Afferent Pathways↗

A code for ponto-geniculo-occipital wave (PGO).

A mechanism of generation of pontine-geniculo-occipital waves (PGO) has been addressed by intra- or extra-cellular recordings from pontine giganto-cellular neurons (PPRF) during various types of vestibular stimulation (cat). PPRF neurons were identified that responded with spike trains ((mean) 8 spike per sec). Statistical treatments of interspike interval and autocorrelation histograms revealed that the response was basically nonrandom. The same PPRF neurons also responded to medium frequency stimulation of excitatory pulse trains released from the medial vestibular nuclei, mainly in cats with enucleated nucleus interstitialis of Cajal and Nucleus Darkschewitsch (NiC, ND) (inhibitory interneurons). Medium frequency MVN activity evoked (generated by REM or by infusion of acetylcholine) the inhibitory activity of interneurons in intact cats. With decreased MVN activity, the inhibition ceased and excitatory pulses were again generated. During REM this process resulted in a cyclic activity with recurring peak-maximums at 3 to 3.5 sec intervals. This cyclic second order vestibular activity reached the PPRF through the medial longitudinal fasciculus together with several other descending vestibular impulses. The special PPRF neurons selectively respond to the cyclic stimuli of second order vestibular nucleus origin with release of the pontine PGO waves. The regularity of the spikes and the interburst intervals are under the control of two different types of pacemaker neurons located near the midline of pons anterior to the PPRF region with 125 msec and 3 to 3.5 sec interpeak intervals respectively. The results suggest that the vestibular system is one of the structures responsible for encoding the PGO waves.

Acetylcholine↗

The active head-impulse test in unilateral peripheral vestibulopathy.

BACKGROUND: The head-impulse test, which is sensitive and specific for detecting severe unilateral peripheral vestibulopathy, is an accepted part of the neurological examination, especially in patients with vertigo and balance disorders. OBJECTIVE: To discover if the head-impulse test is just as useful diagnostically when patients are asked to rotate their own heads, the active head-impulse test, rather than when the clinician does so as in the standard passive head-impulse test. METHODS: Clinical observation of compensatory saccades and search coil measurement of compensatory eye rotations, during active and passive horizontal head-impulses in 6 patients with total unilateral vestibular deafferentation. RESULTS: Clinical observation showed the expected compensatory saccades with rotations toward the side with the lesion with passive head-impulses but not with active head-impulses. Search coil recordings revealed 2 reasons for this. With active head-impulses not only was vestibulo-ocular reflex gain higher, but compensatory saccade latency was shorter resulting in an occult saccade that occurred during, rather than after, head rotation. CONCLUSIONS: Passive head-impulses are necessary to detect a severe unilateral peripheral vestibulopathy; active head-impulses will produce a false-negative result.

Adult↗

Diagnostic value of prolonged latencies in the vestibular evoked myogenic potential.

BACKGROUND: As a parameter for the evaluation of the vestibular evoked myogenic potential (VEMP), amplitude has been used clinically. However, the significance of latency has not been considered. OBJECTIVE: To clarify the diagnostic value of latencies of the VEMP. DESIGN: We reviewed records of the VEMP of patients with various diseases and compared them with records of healthy volunteers. SETTING: Data were collected from patients in an outpatient clinic of a tertiary care center and healthy volunteers. SUBJECTS: Clinical records of 134 patients (61 men and 73 women, aged 20-75 years) were reviewed. Diagnoses were Meniere disease in 43 patients, acoustic neuroma in 62 patients, vestibular neuritis in 23 patients, and multiple sclerosis in 6 patients. Also, 18 healthy volunteers (13 men and 5 women, aged 25-38 years) were enrolled. INTERVENTION: Diagnostic. MAIN OUTCOME MEASURES: Click-evoked myogenic potentials were recorded with surface electrodes over each sternocleidomastoid muscle. Latencies and amplitudes of responses were measured. RESULTS: Vestibular evoked myogenic potentials were absent or decreased in 51% of patients with Meniere disease (n = 22), 39% with vestibular neuritis (n = 9), 77% with acoustic neuroma (n = 48), and 25% with multiple sclerosis (3 of 12 sides of 6 patients). Concerning latency, patients with Meniere disease or vestibular neuritis hardly showed any latency prolongation. Four patients with acoustic neuroma showed prolonged p13; all had large tumors. All patients with multiple sclerosis showed prolonged p13. CONCLUSION: Prolonged latencies of the VEMP suggest lesions in the retrolabyrinthine, especially in the vestibulospinal tract.

Adult↗

Acute vestibular neuritis visualized by 3-T magnetic resonance imaging with high-dose gadolinium.

Sudden idiopathic unilateral loss of vestibular function without other signs or symptoms is called acute vestibular neuritis. It has been suggested that reactivation of human herpes simplex virus 1 could cause vestibular neuritis, Bell palsy, and sudden unilateral hearing loss. Enhancement of the facial nerve on gadolinium-enhanced magnetic resonance imaging (MRI) is a common finding in Bell palsy, but enhancement of the vestibular nerve has never been reported in acute vestibular neuritis. We present 2 consecutive cases of acute vestibular neuritis where high-field-strength MRI (3.0 T) with high-dose (0.3 mmol/kg of body weight) gadolinium-pentetic acid showed isolated enhancement of the vestibular nerve on the affected side only. These findings support the hypothesis of a viral and inflammatory cause of acute vestibular neuritis and might have implications for its treatment.

Aged↗

Metabolic changes in vestibular and visual cortices in acute vestibular neuritis.

Five right-handed patients with a right-sided vestibular neuritis were examined twice with fluorodeoxyglucose positron emission tomography while lying supine with eyes closed: once during the acute stage (mean, 6.6 days) and then 3 months later when central vestibular compensation had occurred. Regional cerebral glucose metabolism (rCGM) was significantly increased (p <0.001 uncorrected) during the acute stage in multisensory vestibular cortical and subcortical areas (parietoinsular vestibular cortex in the posterior insula, posterolateral thalamus, anterior cingulate gyrus [Brodmann area 32/24], pontomesencephalic brainstem, hippocampus). Simultaneously, there was a significant rCGM decrease in the visual (Brodmann area 17 to 19) and somatosensory cortex areas in the postcentral gyrus as well as in parts of the auditory cortex (transverse temporal gyrus). Fluorodeoxyglucose positron emission tomography thus allows imaging of the cortical activation pattern that is induced by unilateral peripheral vestibular loss. It was possible to demonstrate that the central vestibular system including the vestibular cortex exhibits a visual-vestibular activation-deactivation pattern during the acute stage of vestibular neuritis similar to that in healthy volunteers during unilateral labyrinthine stimulation. Contrary to experimental vestibular stimulation, the activation of the vestibular cortex was not bilateral but was unilateral and contralateral to the right-sided labyrinthine failure.

Aged↗

Gamma-aminobutyric acid is present in a spatially discrete subpopulation of hair cells in the crista ampullaris of the toadfish Opsanus tau.

Although gamma-aminobutyric acid (GABA) and glutamate are known to be present in the vestibular sensory epithelia of a variety of species, the functional relationship between these two transmitters is not clear. The present study addresses the three-dimensional spatial distribution of GABA and glutamate immunoreactivity in the vestibular labyrinth of the oyster toadfish by using whole end organs labeled by immunofluorescence with monoclonal anti-GABA and/or antiglutamate antibodies and visualized as whole mounts by multiphoton confocal microscopy. We find glutamate-immunoreactive hair cells present throughout the sensory epithelium. In contrast, prominent GABA immunoreactivity is restricted to a small population of hair cells located in the central region of the crista. Double immunofluorescence reveals two distinct staining patterns in GABA-labeled hair cells. Most ( approximately 80%) GABA-labeled cells show trace levels of glutamate, appropriate for the metabolic/synthetic role of cytoplasmic glutamate. The remainder of the GABA-stained cells contain substantial levels of both GABA and glutamate, suggesting transmitter colocalization. In the toadfish utricle, glutamatergic hair cells are present throughout the macula. GABA-immunoreactive hair cells follow the arc of the striola, and most GABA-labeled receptor cells coexpress glutamate. The localization of GABA was explored in other species as well. In the pigeon, GABAergic hair cells are present throughout the crista ampullaris. Our findings demonstrate that multiple, neurochemically distinct types of hair cells are present in vestibular sensory epithelia. These observations, together with the excitatory activity generally associated with 8th nerve afferent fibers, strongly suggest that GABA serves an important, specific, and complex role in determining primary afferent response dynamics.

Animals↗

Neuroanatomical aspects of the gerbil inner ear: light microscope observations.

A specialization of the Mongolian gerbil inner ear allows easy access for electrophysiological recording from the auditory nerve and other structures of the internal auditory meatus. The round-window membrane is recessed, creating a cavity connecting the bulla and the external wall of the modiolus. This cavity has been named the round-window antrum. A small opening made in the dorsomedial wall of the round-window antrum gives access directly to the modiolus and internal auditory meatus, with no other openings in the cranium required. This surgery is less drastic than that needed for similar access in most other mammals. The anatomy of the specialized region is presented from studies with the light microscope. Emphasis is placed on the relationship between external features of the wall of the round-window antrum and the internal anatomy of the modiolus and internal auditory meatus. In addition, these studies reveal that cell bodies of the acoustic-nerve nucleus are located in the auditory nerve, central to the glial dome. About 22 +/- 8 cells are found in an auditory nerve. Their appearance with a Nissl stain is similar to cells found in rat, mouse, and man. The cell dendrites are preferentially oriented perpendicular to the longitudinal course of the auditory-nerve fibers. The anatomy of the gerbil auditory system should allow direct electrophysiological recording from these cells.

Animals↗

Cytochrome oxidase response to cochlea removal in chicken auditory brainstem neurons.

Changes in cytochrome oxidase (CO) activity were studied in the chick brainstem auditory nuclei, n. magnocellularis (NM) and n. laminaris (NL), following unilateral cochlea removal. Chickens aged 10 days or 56 weeks underwent unilateral cochlea removal. Following survival periods of 30 minutes to 14 days for the 10-day-old birds and 6 hours or 14 days for the 56-week-old birds, the animals were perfused with paraformaldehyde/glutaraldehyde fixative. Cryostat sections of the brainstem were then prepared for CO histochemistry. Microdensitometry was used to quantify the difference in CO staining in NM and NL ipsilateral and contralateral to the cochlea removal. Since the cochlea projects to the ipsilateral NM, the contralateral NM was used as a within-animal control. In normal chickens, NM cell bodies and the cell bodies and dendrites of NL neurons stain darkly for CO in both young and adult birds. In 10-day-old birds, there is no significant change in CO staining in NM from 30 minutes to 3 hours after cochlea removal. Then, a rapid biphasic change in CO staining was found in the ipsilateral NM. An increase in staining was observed 6 to 24 hours postoperatively, followed by a decrease in CO staining at 3- to 14-day survival times. In the 56-week-old birds, no increases in CO staining were observed 6 hours after cochlea removal, but a decrease in CO staining was found 14 days postoperatively. In NL, no changes were observed until 3 days (10-day-old birds) or 14 days (56-week-old birds) after cochlea removal. Then a decrease in CO staining was observed in the dendritic and glial/fiber regions of NL containing axons from the deafferented NM. Thus it appears that afferent input has a regulatory effect on the oxidative metabolism of neurons in the chicken auditory brainstem nuclei, an effect that differs with the age of the animal at the time of afferent manipulation.

Age Factors↗

The alpha9/alpha10-containing nicotinic ACh receptor is directly modulated by opioid peptides, endomorphin-1, and dynorphin B, proposed efferent cotransmitters in the inner ear.

UNLABELLED: Opioid peptides have been detected in the auditory and vestibular efferent neurons where they colocalize with the major neurotransmitter, acetylcholine. We investigated the function of opioids to modulate neurotransmission mediated by hair cell's alpha9/alpha10-containing nicotinic acetylcholine receptors (alpha9/alpha10nAChRs). The endogenous opioid peptides, endomorphin-1 (mu agonist) and dynorphin B (kappa agonist), but not a delta agonist [D-Pen2,D-Pen-5]enkephalin, inhibited the acetylcholine-evoked currents in frog saccular hair cells and rat inner hair cells. This inhibition was noncompetitive, voltage-independent, and was accompanied by an acceleration of the rate of current decay. Selective mu- and kappa-opioid receptor antagonists did not block the inhibition, although partial reduction by naloxone was observed. All opioid antagonists tested also reduced the acetylcholine response. Endomorphin-1 and dynorphin B inhibited the acetylcholine-evoked currents in alpha9/alpha10-expressing Xenopus oocytes. Because oocytes lack opioid receptors, it provides strong evidence for the direct interaction of opioid peptides with alpha9/alpha10nAChR. CONCLUSION: alpha9/alpha10nAChR is a target for modulation by endomorphin-1 and dynorphin B, efferent cotransmitters in the inner ear.

Acetylcholine↗

Associative learning acquisition and retention depends on developmental stage in Lymnaea stagnalis.

Associative learning dependent on visual and vestibular sensory neurons and the underlying cellular mechanisms have been well characterized in Hermissenda but not yet in Lymnaea. Three days of conditioning with paired presentations of a light flash (conditional stimulus: CS) and orbital rotation (unconditional stimulus: UCS) in intact Lymnaea stagnalis results in a whole-body withdrawal response (WBWR) to the CS. In the current study, we examined the optimal stimulus conditions for associative learning, including developmental stage, number of stimuli, interstimulus interval, and intertrial interval. Animals with a shell length longer than 18 mm (sexually mature) acquired and retained the associative memory, while younger ones having a shell length shorter than 15 mm acquired but did not retain the memory to the following day. For mature animals, 10 paired presentations of the CS and UCS presented every 2 min were sufficient for the induction of a WBWR to the CS. Furthermore, animals conditioned with the UCS presented simultaneously with the last 2 s of the CS also exhibited a significant WBWR in response to the CS. Blind animals did not acquire the associative memory, suggesting that ocular photoreceptors, and not dermal photoreceptors, detected the CS. These results show that maturity was key to retention of associative learning.

Animals↗