Transpositional activity of IS986 in Mycobacterium smegmatis

The aim of the present study was to determine if the calcium channel antagonist flunarizine would affect the time course of vestibular compensation for unilateral labyrinthectomy (UL) in guinea pigs. Animals received either a single IP injection of flunarizine 1 h pre-UL or a series of IP injections every 6 h for 24 h post-UL, starting at 6 h post-UL. Flunarizine was dissolved in 50-100% DMSO or suspended in 10% Tween-80 and administered at a dose of 10 mg/kg in the pre-UL condition and 10 or 20 mg/kg in the post-UL condition. All injections were 1 ml/kg in volume. Spontaneous nystagmus (SN), yaw head tilt (YHT), and roll head tilt (RHT) were measured using video analysis. When dissolved in DMSO and administered 1 h pre-UL, 10 mg/kg flunarizine had a small but significant effect on the rate of RHT compensation; otherwise, flunarizine had no significant effects on SN, YHT, or RHT when dissolved in DMSO. When suspended in Tween-80, 10 mg/kg flunarizine pre-UL resulted in a significant decrease in SN frequency and YHT relative to the control group, although the magnitude of the differences was small. When 20 mg/kg was given post-UL, both SN and YHT showed a small but significant change in the rate of compensation. No significant differences in RHT were observed. These results demonstrate that IP administration of flunarizine at a dose of 10-20 mg/kg IP has little effect on vestibular compensation compared to the effects obtained with low IM doses (0.8 mg/kg) of verapamil given 1 h pre-UL.     

The role of tonic vestibular input for postural control in rats

Removal of a vestibular organ deprives the ipsilateral vestibular nuclei of tonic excitatory inflow from vestibular afferents, and thus evokes a central asymmetry, that is imbalance between tonic activity of the left and right vestibular nuclear complexes. In the present study, the effect of the central asymmetry upon a function of different motor systems was investigated in the freely behaving rats subjected to unilateral or bilateral labyrinthectomy (UL or BL). In four sets of experiments the following results have been obtained. 1. Seven UL-evoked symptoms (which reflect impairment of different motor systems) were qualitatively characterized. The short-lasting symptoms were: (1) body twisting, (2) rolling, (3, 4) extension of the fore- and hindlimb contralateral to UL, and (5) circling. These symptoms disappeared in a fixed order during recovery from anesthesia. During of expression of the symptoms was very short (< 1 hour) with the Halothan anesthesia and much longer (approximately 8 hours) with the chloral hydrate anesthesia. The long-lasting symptoms were (6) spontaneous ocular nystagmus, that persisted for 3 days after UL, and (7) head roll tilt, that persisted for at least several weeks after UL. 2. In BL-animals, stimulation of one of the 8th nerves was performed (by means of an implanted electrode; pulses 0.3 ms, 50 Hz, current up to 400 microA). By increasing gradually the strength of the stimulating current, we could evoke all the UL-symptoms but generally in the order (7-->1) which was the reverse as compared to the order of disappearance of the corresponding symptoms during recovery after UL (1-->7). These findings suggest that different symptoms need different levels of the central asymmetry for their appearance, and these levels also determine the order of disappearance of the symptoms during recovery from UL. 3. In UL-animals, by stimulating the 8th nerve on UL-side with a properly adjusted current (200-400 microA) we could immediately abolish all the symptoms except (6), which was, however, considerably reduced. This finding suggests that stimulation of the 8th nerve in UL-rats restores the central symmetry, which results in a concerted disappearance of almost all symptoms. In addition to the intermediate effects, stimulation of the 8th nerve in UL-animals resulted in a long-lasting effect, that is a reduction of the head roll tilt which persisted for at least 10 days after stimulation. 4. In BL-animals bilateral stimulation of the 8th nerve resulted in restoration of the muscular tone, and in considerable improvement of the control of the head position.     

Uncrossed disynaptic inhibition of second-order vestibular neurons and its interaction with monosynaptic excitation from vestibular nerve afferent fibers in the frog

1. Eighth nerve evoked responses in central vestibular neurons (n = 146) were studied in the isolated brain stem of frogs. Ninety percent of these neurons responded with a monosynaptic excitatory postsynaptic potential (EPSP) after electrical stimulation of the ipsilateral VIIIth nerve. In 5% of these neurons, the EPSP was truncated by a disynaptic inhibitory postsynaptic potential (IPSP), and in 5% of these neurons a pure disynaptic IPSP was evoked. 2. Disynaptic IPSPs superimposed upon apparently pure EPSPs were revealed by bath application of the glycine receptor antagonist strychnine (0.5-5 microM) or of the gamma-aminobutyric acid-A (GABAA) receptor antagonist bicuculline (0.5-2 microM). The evoked EPSP increased in most central vestibular neurons (strychnine: 15 out of 16 neurons; bicuculline 26 out of 29 neurons). At higher stimulus intensities, the evoked spike discharge increased from 2 to 3 spikes before up to 8-10 spikes per electrical pulse during the application of blocking agents. The unmasked disynaptic inhibitory component increased with stimulus intensity to a different extent in different neurons. 3. Lesion studies demonstrated that these inhibitory components were generated ipsilaterally with respect to the recording side. The disynaptic strychnine-sensitive inhibition was mediated by neurons located either in the ventral vestibular nuclear complex (VNC) or in the adjacent reticular formation. The spatial distribution of the disynaptic inhibition was investigated by simultaneous recordings of VIIIth nerve-evoked field potentials at different rostrocaudal locations of the VNC. A significant strychnine-sensitive component was detected in the middle and caudal parts but not in the rostral part of the VNC. A bicuculline-sensitive component was detected in the rostral and in the caudal parts but not in the middle part of the VNC. In view of a similar rostrocaudal distribution of glycineor GABA-immunoreactive neurons in the VNC of frogs, our results suggest that part of the disynaptic inhibition is mediated by local interneurons with a spatially restricted projection area. 4. The monosynaptic EPSP of second-order vestibular neurons was mediated in part by N-methyl-D-aspartate (NMDA) and in part by non-NMDA receptors. The relative contribution of the NMDA receptor-mediated component of the EPSP decreased with stronger stimuli. This negative correlation could have resulted from a preferential activation of NMDA receptors via thick vestibular nerve afferent fibers. Alternatively, the activation of NMDA receptors became disfacilitated at higher stimulus intensities due to the recruitment of disynaptic inhibitory inputs. Comparison of data obtained in the presence and in the absence of these glycine and GABAA receptor blockers indicates a preferential activation of NMDA receptors via larger-diameter vestibular nerve afferent fibers. 5. The kinetics of NMDA receptors (delay, rise time) activated by afferent nerve inputs were relatively fast. These fast kinetics were independent of superimposed IPSPs. The association of these receptors with large-diameter vestibular nerve afferent fibers suggests that fast NMDA receptor kinetics might be matched to the more phasic response dynamics of the large diameter vestibular afferent neurons to natural head accelerations.     

Comparative approaches to the avian song system

The aim of this paper is to: i) review the behavioural, electrophysiological, pharmacological and biochemical evidence relating to the involvement of N-methyl-D-aspartate (NMDA) receptors in the vestibular compensation process which follows unilateral peripheral vestibular deafferentation (UVD); and ii) suggest a unifying hypothesis based on this literature and recent studies of long-term depression (LTD)-like phenomena in the brainstem vestibular nucleus complex (VNC). It is suggested that NMDA receptors may induce a form of heterosynaptic LTD in the ipsilateral VNC, which is partly responsible for the extent of the hypoactivity which occurs immediately following UVD, and the severity of the associated vestibular syndrome. It is also suggested that vestibular compensation may develop as this LTD dissipates, allowing remaining synaptic inputs and the intrinsic properties of ipsilateral VNC neurons to re-establish the resting activity which is responsible for static vestibular compensation. It is argued that this hypothesis accounts for the majority of the available data on NMDA receptors in relation to vestibular compensation, and may serve as a useful working hypothesis, in order to formulate further experiments to investigate the contribution of NMDA receptors to the compensation process.     

Effects of MK801 on Fos expression in the rat brainstem after unilateral labyrinthectomy

Unilateral labyrinthectomy (UL) causes ocular and postural asymmetries, which disappear over time in the processes of equilibrium recovery known as vestibular compensation. It has been reported that N-methyl-D-aspartate (NMDA) receptors are involved in vestibular compensation. In the present study, in order to elucidate the NMDA receptor-mediated neural circuit responsible for the development of vestibular compensation, we used Fos expression as a marker of neural activation and examined the effects of MK801, a specific antagonist of NMDA receptors, on UL-induced Fos expression in the rat brainstem. After UL, Fos-like immunoreactive (-LIR) neurons were observed in the ipsilateral medial vestibular nucleus (ipsi-MVe), the contralateral prepositus hypoglossal nucleus (contra-PrH) and the contralateral inferior olive beta subnucleus (contra-IOb). Fos-LIR neurons gradually disappeared in the processes of vestibular compensation. It is suggested that the activation of the ipsi-MVe, the contra-PrH and the contra-IOb neurons after UL are the initial event of vestibular compensation. Intraperitoneal injection of MK801 in the processes of vestibular compensation caused reappearance of UL-induced behavioral deficits. During the decompensation induced by MK801, Fos-LIR neurons appeared in the contra-MVe, the ipsi-PrH and the bilateral-IOB. It is suggested that the contra-MVe, the ipsi-PrH and the bilateral-IOb neurons are inhibited by glutamatergic synapses driving inhibitory neurons via NMDA receptors in the processes of vestibular compensation and that disinhibition of these nuclei induced by MK801 causes decompensation. However, MK801 caused neither Fos expression nor behavioral decompensation after vestibular compensation is accomplished. All these findings that the NMDA receptor-mediated inhibitory modulation in the central vestibular system plays an important role for the initial processes of the development of vestibular compensation.     

Polyamines increase in the brain stem and cerebellum following labyrinthectomy

The goal of this investigation was to test the hypothesis that unilateral damage to the vestibular end-organ (labyrinthectomy) stimulates polyamine synthesis in central vestibular neural structures that mediate the process of behavioral recovery (vestibular compensation). Pharmacological studies have shown that compensation can be altered by alpha-difluoromethylornithine (DFMO), a specific inhibitor of polyamine synthesis. Because polyamines are important in regeneration, development and modulation of N-methyl-D-aspartate (NMDA) excitatory amino acid receptors, which mediate vestibular synaptic plasticity, we investigated changes in polyamines in specific central vestibular structures after unilateral labyrinthectomy. The supernatant fraction of brain tissue homogenates was reacted with dansyl chloride. Dansylated polyamine derivatives were quantified in the vestibular nuclei, cerebellum, and inferior olive in both the control and the unilaterally labyrinthectomized guinea pig by high-performance liquid chromatography-fluorometric detection. No left-right differences in putrescine, spermidine, or spermine were detected in any brain parenchyma of controls. Polyamine imbalance, characterized by increased spermidine in the ipsilateral medial and lateral vestibular nuclei, was noted 12 and 24 h after unilateral labyrinthectomy (UL). In contrast, spermidine, spermine, and putrescine were elevated bilaterally in the cerebellum and inferior olive after UL. These biochemical changes may represent neuronal modifications to establish a balance between the vestibular nuclei after unilateral labyrinthectomy. Elucidation of the role of polyamines in central vestibular function and in vestibular compensation offers promise for the development of novel therapeutic strategies for treatment of vestibular disorders.     

Prevention of vestibular deafferentation-induced spontaneous nystagmus with pretreatment of Ca2+ channel/N-methyl-D-aspartic acid receptor antagonists in guinea pigs

Involvement of Ca2+ channel and N-methyl-D-aspartic acid (NMDA) receptors with induction of the spontaneous nystagmus (SN) after unilateral labyrinthectomy (UL) was evaluated by examining the effect of verapamil and MK-801 in guinea pigs. An injection of verapamil or MK-801 before the intratympanic application of arsanilate significantly (p < 0.05) suppressed the frequency of the SN towards the arsanilate-applied side. The frequency of the SN towards the intact side in these drug-treated animals was much lower than in the control animals until 36 h after the application of arsanilate. In addition, 60 days subsequent to induction of the UL, application of the drug before we injected the arsanilate into the opposite middle ear suppressed the SN towards the second arsanilate-injected side, but not towards the first injection side. We suggest that Ca2+ channel and NMDA receptor may be involved in the induction of the SN, and that the pretreatment of their antagonists could be applied in preventing the vestibular deafferentation-induced SN.     

Melanocortin analogue Org2766 binds to rat Schwann cells, upregulates NGF low-affinity receptor p75, and releases neurotrophic activity

Binding of the stable melanocortin(4-9) analogue, Org2766 [Met(O2)-Glu-His-Phe-D-Lys-Phe] to cultured rat sciatic nerve Schwann cells was demonstrated using a biotinylated derivative in semiquantitative histochemical and CELISA assays. Org2766 bound to Schwann cells, but not to fibroblasts, and was displaced maximally by unlabeled Org2766, alpha-MSH and ACTH(1-24). Displacement of Org2766 from the binding sites was considerably reduced by N- and C-truncation of the peptide. Specific binding of Org2766 was also demonstrated in the immortal rat Schwann cell line SCL4.1/F7 and was more pronounced in cells displaying a differentiated morphology. Org2766 and alpha-MSH increased cyclic AMP content of Schwann cells but neither stimulated DNA synthesis when applied alone. However, in the presence of a priming (subthreshold) concentration of the mitogen, cholera toxin, Org2766 and alpha-MSH caused a delayed increase in DNA synthesis. Org2766 did not modulate the expression of several differentiation-related Schwann cell markers. However, Org2766 increased immunoreactivity for p75 low-affinity NGF receptor on Schwann cells and evoked the release of neurotrophic factor(s) that synergized with NGF in stimulating neurite outgrowth in rat DRG neurons. The results indicate that Schwann cells are a primary target for the action of Org2766 and provide evidence for an indirect mechanism by which melanocortins might stimulate neurite sprouting in regenerating peripheral nerve axons.     

Brachytherapy in early prostate cancer--early experience

Intravenous lidocaine has been reported to alleviate vertigo in Meniere's disease and suggested as a possible antivertigo agent after unilateral labyrinthectomy in a study of cats. To further evaluate the effects of intravenous lidocaine on the acute phase of postural compensation, we subjected 13 pigmented guinea pigs to unilateral labyrinthectomy. Seven received intravenous lidocaine (4 mg/kg) immediately after labyrinthectomy. The other six served as controls and received an equivalent-volume injection of normal saline solution. Total body curvature, trunk curvature, yaw head tilt, and roll head tilt were measured at frequent intervals for up to 30 hours after surgery. Both groups had immediate difficulties with posturing that gradually improved. The lidocaine group tended to exhibit delayed postural compensation, but this was only statistically significant for roll head tilt. These results do not show improvement in postural compensation from unilateral labyrinthectomy after the administration of intravenous lidocaine. A species-specific effect on the vestibular pathways is suggested, and we conclude that further evaluation of lidocaine and the vestibular system is warranted.     

Polyamine changes in the vestibular nuclei of guinea pigs following labyrinthectomy

Vestibular compensation is a process of behavioral recovery from ocular, motor and postural disorders following unilateral damage to the vestibular end-organ. Although restoration of the normal resting discharge rate in the ipsilateral vestibular nuclei is important in compensation, the biochemical and molecular mechanisms mediating recovery are largely unknown. The ornithine decarboxylase polyamine pathway is activated in the nervous system following axotomy or denervation. The authors postulate that changes in polyamines mediate vestibular compensation. Within 150-micron brain stem coronal section micropunches analyzed by high performance liquid chromatography techniques, the polyamine spermidine was significantly increased in the ipsilateral lateral vestibular nucleus 8 hours following labyrinthectomy in the guinea pig model. Because naturally occurring polyamines modulate excitatory amino acid receptors (N-methyl-D-aspartate [NMDA]) which in turn mediate neurotransmission between primary afferents and second order vestibular neurons, stimulation of polyamine pathways following neural injury may play a critical role in compensation.     

Intrahepatic gas formation without abscess after hepatic artery thrombosis in the setting of liver transplantation

This paper reports that lesions of the medial frontal cortex (MFC) caused behavioral deficit in rats and that this deficit could be attenuated by a well formulated treatment with Org2766, an analog of ACTH-(4-9). Wistar rats were distributed in 3 groups: MFC lesion treated with saline (M-N); MFC lesion treated with Org2766 (M-O); and sham-operation treated with saline (S). Repeated Org2766 or saline injection commenced from the day of surgery and lasted for 13 days. After surgery, the rats were trained in a passive avoidance task and then in an active avoidance task. MFC lesions were found to be strongly associated with behavioral deficits. The M-N group rats displayed poor retention of the passive avoidance response and showed much slower learning of the active avoidance task as compared to S group rats. The result showed that chronic Org2766 administration improved the behavioral performance of both tasks in MFC lesioned rats. The also revealed that the superoxide dismutase (SOD) activity was significantly increased in the M-O group as compared to the M-N group 15 days after surgery. The possible mechanisms related to the beneficial effect of Org2766 on cortex damage are discussed.     

Role of primate medial vestibular nucleus in long-term adaptive plasticity of vestibuloocular reflex

1. Fifteen hundred and thirty cells were recorded in the medial vestibular nucleus (MVN) of alert monkeys whose vestibuloocular reflex (VOR) had been adapted to one of two kinds of spectacles. The "high-gain" sample was recorded from monkeys that had worn 2.0 x telescopic spectacles; the gain of the VOR in the dark (eye velocity divided by head velocity) was greater than 1.5. The "low-gain" sample was recorded from monkeys that had worn goggles providing a visual field that was fixed with respect to the freely turning head; the gain of the VOR was less than 0.4. 2. Cells showing modulation of firing rate related to imposed head velocity were grouped into four categories: pure vestibular (10), vestibular-plus-saccade (10), vestibular-plus-position (10), and vestibular-plus-head/body (24). Sensitivity to head velocity was measured from averaged responses to sinusoidal, 0.4-Hz whole-body oscillation in the horizontal plane. Almost all cells (98%) having increased firing during ipsilateral head rotation received inputs from the horizontal semicircular canals. Conversely, 82% of cells having increased firing during contralateral head rotation received inputs from the vertical canals. 3. There were no statistically significant differences in resting discharge rate, phase shift, or sensitivity to head velocity between the high- and low-gain samples of any of the cell types. Nonetheless, there was a consistent tendency, evident in all the functionally defined cell groups, for the sensitivity to be about 20% greater in the high-gain samples. However, this difference is small by comparison with the fourfold difference in VOR gain. 4. Detailed scrutiny of the response properties of individual cells suggested that the small differences in sensitivity reflect small changes distributed throughout the population, rather than large and potentially significant changes within a small sub-population. 5. Our data indicate that large, adaptive changes in the gain of the VOR are accompanied by only minor changes in the vestibular sensitivity and no changes in the phase shift or resting discharge rates of cells in the MVN. It remains possible that large changes in vestibular sensitivity occurred in cells we did not sample or in subgroups we could not identify. We argue that this is unlikely and that the major changes underlying VOR plasticity occur after the first central synapse in the VOR pathways.     

Assessment of vestibular function by videonystagmoscopy

Videonystagmoscopy has been used to subjectively observe the responses of the vestibular system in a population of patients with vestibular deficits. These results were compared with those of a control group of healthy, age-matched volunteers. The videonystagmoscopy device is made of one or two CCD cameras mounted on lightproof goggles, allowing a subjective observation of ocular movements on a video monitor. The eye movements, as well as the position of the head in space, can be recorded on videotape. The eyes are illuminated by infrared light emitting diodes placed on each side of the camera lens. The subjects are seated on a manually driven Barany chair. Subjects went through a protocol of passive roll head tilt on each side, followed by a slow, whole body rotation of 180 degrees amplitude, clockwise and counterclockwise, and then a head shaking test (HST). The eyes were subjectively observed, and we focussed on: torsional eye movements during head tilt, nystagmus when the rotation had stopped, and nystagmus induced by HST. With this simple and noninvasive examining procedure, screening of vestibular function at the bedside or during E.N.T. clinical investigations is possible.     

Distribution of GABA, glycine, and glutamate immunoreactivities in the vestibular nuclear complex of the frog

This study describes the localization of gamma-aminobutyric acid (GABA), glycine, and glutamate immunoreactive neurons, fibers, and terminal-like structures in the vestibular nuclear complex (VNC) of the frog by using a postembedding procedure with consecutive semithin sections at the light microscopic level. For purposes of this study, the VNC was divided into a medial and lateral region. Immunoreactive cells were observed in all parts of the VNC. GABA-positive neurons, generally small in size, were predominantly located in the medial part of the VNC. Glycine-positive cells, more heterogeneous in size than GABA-positive cells, were scattered throughout the VNC. A quantitative analysis of the spatial distribution of GABA glycine immunoreactive cells revealed a complementary relation between the density of GABA and glycine immunoreactive neurons along the rostrocaudal extent of the VNC. In about 10% of the immunolabeled neurons, GABA and glycine were colocalized. Almost all vestibular neurons were, to a variable degree, glutamate immunoreactive, and colocalization of glutamate with GABA and/or glycine was typical. GABA, glycine, or glutamate immunoreactive puncta were found in close contact to somata and main dendrites of vestibular neurons. A quantitative analysis revealed a predominance of glutamate-positive terminal-like structures compared to glycine or GABA containing profiles. A small proportion of terminal-like structures expressed colocalization of GABA and glycine or glycine and glutamate. The results are compared with data from mammals and discussed in relation to vestibuloocular and vestibulo-spinal projection neurons, and vestibular interneurons. GABA and glycine are the major inhibitory transmitters of these neurons in frogs as well as in mammals. The differential distribution of GABA and glycine might reflect a compartmentalization of neurons that is preserved to some extent from the early embryogenetic segmentation of the hindbrain.     

Transient changes in flocculonodular lobe protein kinase C expression during vestibular compensation

Protein kinase C (PKC) is a family of intracellular signal transduction enzymes, comprising isoforms that vary in sensitivity to calcium, arachidonic acid, and diacylglycerol. PKC isoforms alpha, gamma, and delta are expressed by cerebellar Purkinje cells and neurons in the cerebellar nuclei and vestibular nuclei of the Long-Evans rat. In control rats, these PKCs are distributed symmetrically in the flocculonodular-lobe Purkinje cells. Behavioral recovery from vestibular dysfunction produced by unilateral labyrinthectomy (UL) is accompanied by asymmetric expression of PKC isoforms in these regions within 6 hr after UL. These expression changes were localized within parasagittal regions of the flocculus and nodulus. The distribution of PKCalpha, -gamma, and -delta were identical, suggesting that they are coregulated in cerebellar Purkinje cells during this early compensatory period. The pattern of Purkinje cell PKC expression returned to the control, symmetric distribution within 24 hr after UL. It is hypothesized that these regional changes in Purkinje cell PKC expression are an early intracellular signal contributing to vestibular compensation. In particular, regulation of PKC expression may contribute to changes in the efficacy of cerebellar synaptic plasticity during the acute post-UL period.     

Rostral fastigial nucleus activity in the alert monkey during three-dimensional passive head movements

The fastigial nucleus (FN) receives vestibular information predominantly from Purkinje cells of the vermis. FN in the monkey can be divided in a rostral part, related to spinal mechanisms, and a caudal part with oculomotor functions. To understand the role of FN during movements in space, single-unit activity in alert monkeys was recorded during passive three-dimensional head movements from rostral FN. Seated monkeys were rotated sinusoidally around a horizontal earth-fixed axis (vertical stimulation) at different orientations 15 degrees apart (including roll, pitch, vertical canal plane and intermediate planes). In addition, sinusoidal rotations around an earth-vertical axis (yaw stimulus) included different roll and pitch positions (+/-10 degrees, +/-20 degrees). The latter positions were also used for static stimulation. One hundred fifty-eight neurons in two monkeys were modulated during the sinusoidal vertical search stimulation. The vast majority showed a uniform response pattern: a maximum at a specific head orientation (response vector orientation) and a null response 90 degrees apart. Detailed analysis was obtained from 111 neurons. On the basis of their phase relation during dynamic stimulation and their response to static tilt, these neurons were classified as vertical semicircular canal related (n = 79, 71.2%) or otolith related (n = 25; 22.5%). Only seven neurons did not follow the usual response pattern and were classified as complex neurons. For the vertical canal-related neurons (n = 79) all eight major response vector orientations (ipsilateral or contralateral anterior canal, posterior canal, roll, and nose-down and nose-up pitch) were found in Fn on one side. Neurons with ipsilateral orientations were more numerous and on average more sensitive than those with contralateral orientations. Twenty-eight percent of the vertical canal-related neurons also responded to horizontal canal stimulation. None of the vertical canal-related neurons responded to static tilt. Otolith-related neurons (n = 25) had a phase relation close to head position and were considerably less numerous than canal-related neurons. Except for pitch, all other response vector orientations were found. Seventy percent of these neurons responding during dynamic stimulation also responded during static tilt. The sensitivity during dynamic stimulation was always higher than during static stimulation. Sixty-one percent of the otolith-related neurons responded also to horizontal canal stimulation. These results show that in FN, robust vestibular signals are abundant. Canal-related responses are much more common than otolith-related responses. Although for many canal neurons the responses can be related to single canal planes, convergence between vertical canals but also with horizontal canals is common.     

Functional characterization of primary vestibular afferents in the frog

1. In order to more accurately identify the nature of the vestibular input to central neurons, the response properties of single semicircular canal and otolith units in the frog VIIth nerve were studied in curarized preparations. 2. An equation describing the response plane was calculated for each canal on the basis of null point measurements. These results show that the ipsilateral canal planes are orthogonal within 2-5 degrees, and the pairs of right-left synergists are essentially coplanar. A head position of 10-20 degrees maxilla nose up produces optimal horizontal canal and minimal vertical canal activation with horizontal rotation. 3. The frequency response of the horizontal canal was examined in the range 0.025-0.5 Hz. Comparatively shorter phase-lags and a 10 fold greater acceleration gain in this frequency range distinguish the frog from the mammalian species studied. 4. Otolithic responses were tonic, phasic-tonic, and phasic in nature. The preponderance of the latter two groups is stressed (94%). Tonic responses were proportional to the gravitational vector change. Phasic responses were proportional to velocity during transitions in head position and phase-led displacement (30-80%) with sinusoidal acceleration in roll and pitch. 5. Efferent vestibular neurons respond to rotation in the horizontal (usually Type III) as well as vertical planes. Responses in the vertical planes result from canal and/or otolithic input to these neurons indicating that the vestibular efferent system receives extensive multi-labyrinthine convergence.     

Endoscope-assisted vestibular neurectomy

OBJECTIVE/HYPOTHESIS: In some instances endoscopes offer better visualization than the microscope and frequently allow less invasive surgery. This study was undertaken to determine whether endoscopy is safe and effective during neurectomy of the vestibular nerve. METHOD: Ten patients with intractable unilateral Meniere's disease underwent a retrosigmoid craniotomy for neurectomy of the vestibular nerve. Endoscopy with a Hopkins telescope was used during each procedure to study posterior fossa anatomic relationships and to assist the neurectomy. Preoperative and postoperative audiometric evaluation was performed in all patients undergoing vestibular neurectomy. Nine of these patients had preoperative electronystagmography, and four patients completed postoperative electronystagmography. The 1995 American Academy of Otolaryngology-Head and Neck Surgery's Committee on Hearing and Equilibrium guidelines for the diagnosis and evaluation of therapy in Meniere's disease were used. RESULTS: Complete neurectomy was achieved in all 10 patients. Endoscopy allowed improved identification of the nervus intermedius and the facial, cochlear, and vestibular nerves and adjacent neurovascular relationships without the need for significant retraction of the cerebellum or brainstem. In addition, endoscopic identification of the cleavage plane between the cochlear and vestibular nerves medial to or within the internal auditory canal (n = 3) was not made with the 0-degree endoscope; however, identification was made with the 30- or 70-degree endoscope in all cases. In all patients with Meniere's disease, elimination of the recurrent episodes of vertigo (n = 10) or otolithic crisis of Tumarkin (n = 1) was achieved. CONCLUSIONS: Posterior fossa endoscopy can be performed safely. Endoscope-assisted neurectomy of the vestibular nerve may offer some advantages over standard microsurgery including increased visualization, more complete neurectomy, minimal cerebellar retraction, and a lowered risk of cerebrospinal fluid leakage.     

Spontaneous activity of otolith-related vestibular nuclear neurons in the decerebrate rat

The discharge properties of lateral and descending vestibular neurons responsive to constant velocity off-vertical axis rotations (OVAR) in the clockwise (CW) and counterclockwise (CCW) directions, were studied at the stationary and earth-horizontal position of decerebrate adult rats. From the coefficient of variation (CV), the spontaneous activities of OVAR-responsive neurons were classified into regular and irregular patterns. Of the neurons (n = 36) that showed symmetric and stable bidirectional response sensitivity (delta defined as CW gain over CCW gain) to OVAR (10 degrees tilt), some exhibited progressive phase shift with velocity (1.75-15 degrees/s) while others exhibited stable response phase. Most neurons of the former group (93% or 12/13) showed regular discharge pattern while only 22% (n = 5/23) of the latter group showed such a pattern. Though the phase-stable neurons showed a significantly higher average CV than the phase-shifted neurons, there was no significant difference between the mean spontaneous firing rates of these neurons. The neurons (n = 17) that showed asymmetric and variable delta to OVAR velocity can also be grouped-those that exhibited a greater gain with rotations directed towards the side of recording (I neurons) showed irregular discharge pattern while those that exhibited a greater gain with rotations directed towards the side contralateral to recording (C neurons) showed regular discharge pattern. The I and C neurons also exhibited significant difference in mean firing rates. The relationship between the response characteristics of the OVAR-responsive neurons and their spontaneous activity at the stationary and earth-horizontal position is discussed.