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Static and dynamic properties of synaptic transmission at the cyto-neural junction of frog labyrinth posterior canal.

The properties of synaptic transmission have been studied at the cyto-neural junction of the frog labyrinth posterior canal by examining excitatory postsynaptic potential (EPSP) activity recorded intraaxonally from the afferent nerve after abolishing spike firing by tetrodotoxin. The waveform, amplitude, and rate of occurrence of the EPSPs have been evaluated by means of a procedure of fluctuation analysis devised to continuously monitor these parameters, at rest as well as during stimulation of the semicircular canal by sinusoidal rotation at 0.1 Hz, with peak accelerations ranging from 8 to 87 deg.s-2. Responses to excitatory and inhibitory accelerations were quantified in terms of maximum and minimum EPSP rates, respectively, as well as total numbers of EPSPs occurring during the excitatory and inhibitory half cycles. Excitatory responses were systematically larger than inhibitory ones (asymmetry). Excitatory responses were linearly related either to peak acceleration or to its logarithm, and the same occurred for inhibitory responses. In all units examined, the asymmetry of the response yielded nonlinear two-sided input-output intensity functions. Silencing of EPSPs during inhibition (rectification) was never observed. Comparison of activity during the first cycle of rotation with the average response over several cycles indicated that variable degrees of adaptation (up to 48%) characterize the excitatory response, whereas no consistent adaptation was observed in the inhibitory response. All fibers appeared to give responses nearly in phase with angular velocity, at 0.1 Hz, although the peak rates generally anticipated by a few degrees the peak angular velocity. From the data presented it appears that asymmetry, adaptation, and at least part of the phase lead in afferent nerve response are of presynaptic origin, whereas rectification and possible further phase lead arise at the encoder. To confirm these conclusions a simultaneous though limited study of spike firing and EPSP activity has been attempted in a few fibers.

Action Potentials↗

Genetics of polycystic ovary syndrome: searching for the way out of the labyrinth.

Polycystic ovary syndrome (PCOS) is a complex and heterogeneous disorder presenting a challenge for clinical investigators. It is the most common endocrine disorder of women in reproductive age, a multifaceted reproductive, cosmetic and metabolic problem, with an enigmatic pathophysiological and molecular basis. Although the familial segregation has been noticed very early in the description of the syndrome and family studies in first-degree relatives of women diagnosed with PCOS reveal clustering of the disease, the genetic studies have not as yet determine the pattern of heredity. Part of the problem in genetic studies has been the lack of uniform criteria for diagnosis, heterogeneity of phenotypic features and the fact that the disorder is only expressed clinically in women during their reproductive years. Even within affected families and between sisters with polycystic ovaries, there is heterogeneity in presentation. However, regardless of diagnostic criteria used to identify profanes and to determine affected status in the kindred, the foundation of genetic studies suggests a strong familial component. Currently, PCOS is considered a polygenic trait that might result from the interaction of susceptible and protective genomic variants under the influence of environmental factors, whose role is under intensive investigation. Candidate genes cover a broad spectrum of an endless list of molecules which participate on every step of reproductive and metabolic pathways of this syndrome. Focused research in identification of these genes may provide valuable information and shed some light on the way out of the genomic labyrinth, elucidating the underlying pathophysiology and aiming at a more efficient therapeutic approach of this complicated endocrine disorder.

Animals↗

Magnetic resonance imaging of the membranous labyrinth during in vivo gadolinium (Gd-DTPA-BMA) uptake in the normal and lesioned cochlea.

MRI with a T1 contrast agent was used to investigate the normal and noise-damaged cochlea. The time course and distribution of the in vivo uptake of the gadodiamide chelate bound paramagnetic Gd ion (GdDTPA-BMA) throughout the membranous labyrinth of normal and impulse noise-damaged guinea pig cochleae were measured by MRI at 4.7T. Simultaneous signal enhancement of the basal, medial and apical scala tympani (ST) and scala vestibuli (SV) was observed within 10 min following i.v. injection, reaching maximum levels at around 100 min. ANOVA and post hoc paired t-tests showed statistically significant differences in the levels and rates of Gd uptake-enhancement between the scalae. The ST revealed the most rapid and extensive enhancement throughout the period of active Gd uptake, while the SV showed comparatively slower and less enhancement, and the intact scala media (SM) indicated insignificant enhancement. The in vivo Gd penetration and enhancement of the membranous SM increased significantly in the noise-damaged cochlea, suggesting lesioning of the cochlear membranes.

Acoustic Stimulation↗

Tuning in caudal fastigial nucleus units during natural and galvanic labyrinth stimulation.

Neurons of the caudal fastigial nucleus were investigated by means of single unit recordings. Natural vestibular stimuli were applied as well as galvanic labyrinth polarization. One-third of the neurons showed a convergence of vertical and horizontal canals. More than 80% of the neurons responded to polarization of both the ipsilateral and contralateral canals (binaural responders). Most neurons had a limited response range. Two classes of neurons could be distinguished: up to 1 Hz responders and up to 10 Hz responders. In addition a group of fastigial cells showed a tuning within a small range of frequencies (sharp-tuning responders).

Action Potentials↗

Basal membrane labyrinths in the healing stages of chick nutritional encephalopathy.

Chicks were fed a diet rich in oxidized oil and deficient in alpha-tocopherol. As soon as nutritional encephalopathy developed the animals were immediately put on to a normal diet, and kept alive for up to 166 days. Examination of the cerebellum showed multiple foci of healed encephalomalacia with EM appearance of basal membrane labyrinths between astroglial cells and around blood vessels. The possible origin of the basement membrane material in this conditions was considered and compared with similar formations in normal animals, in CNS tumour explants, and after portocaval anastomosis as well as after spinal cord lesions.

Animals↗

Exercise and drug therapy alter recovery from labyrinth lesion in humans.

Acute unilateral vestibular failure is characterized by rotatory vertigo, horizontal-rotatory nystagmus, and postural imbalance, all of which last from days to weeks. These signs and symptoms are caused by a vestibular tone imbalance between the two labyrinths. Recovery results from a combination of peripheral restoration of labyrinthine function (usually incomplete) and central vestibular compensation (CVC) of the vestibular tone imbalance. Acute unilateral failure is most often caused by vestibular neuritis, which is most likely due to the reactivation of a latent HSV-1 infection. Therefore, therapeutic strategies to improve the outcome of VN are theoretically based on two principles: (a) vestibular exercises and drugs to improve CVC and (b) drug treatment of the assumed viral inflammation. The following conclusions can be drawn from studies in animals and/or humans: (1) There is strong evidence that vestibular exercises may improve vestibulo-spinal compensation. These exercises should begin as early as possible after symptom onset. Moreover, slower exercises are likely to be more effective than faster exercises because slower ones seem to depend more on the vestibular system. (2) Despite extensive data from animal experiments indicating that drugs have a favorable effect on CVC, this has not been clinically proven and thus cannot be recommended yet. (3) Preliminary results of an interim analysis from an ongoing randomized, prospective study showed that methylprednisolone (plus an antiviral agent?) may be useful for improving peripheral vestibular function in vestibular neuritis.

Acyclovir↗

Histochemical and biochemical studies of cholinesterases in the carotid labyrinth of amphibians.

Acetylcholinesterase activity was detected in the carotid labyrinth of amphibians by both biochemical and histochemical methods. The histochemical tests showed enzyme activity in surfaces of afferent and efferent nerve terminals in contact with type I cells, but none within the type I cells. Acetylcholinesterase activity occurred on some, though not all, nerve fibers in the extra-cellular spaces. These fibers might be parasympathetic cholinergic fibers innervating blood vessels.

Acetylcholinesterase↗

Responses of medullary reticulospinal neurons to sinusoidal stimulation of labyrinth receptors in decerebrate cat.

The electrical activity of 168 individual neurons located in the medullary reticular formation, namely, in the medial aspects of the nucleus reticularis gigantocellularis, magnocellularis, and ventralis, has been recorded in precollicular decerebrate cats during sinusoidal tilt about the longitudinal axis of the whole animal, leading to stimulation of labyrinth receptors. In particular, 93 neurons were activated antidromically by stimulation of the spinal cord at T12 and L1 (1RS neurons); the remaining 75 neurons were not activated antidromically (RF neurons). Among these medial reticular neurons tested, 64 of 93 (i.e., 69%) 1RS neurons and 49 of 75 (i.e., 65%) 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 10 degrees. A periodic modulation of firing rate of the units was observed during the sinusoidal stimulus. In particular, 71 of 113 units (i.e., 63%) were excited during side-up and depressed during side-down tilt, whereas 24 of 113 units (i.e., 21%) showed the opposite behavior. In both instances, the peak of the responses occurred with an average phase lead of about +25 degrees with respect to the extreme side-up or side-down position of the animal. The remaining 18 units (i.e., 16%) showed a prominent phase shift of the peak of their response with respect to animal position. Within the explored region of the medulla, the proportion of units excited during side-up tilt was higher at caudal levels, whereas that of the units excited during side-down tilt was higher at rostral levels. Units displaying intermediate phase angle of the responses predominated at intermediate levels of the medulla. Responses to animal tilt were detectable at 1 degree of peak displacement. The gain (impulses x s-1 x deg-1) of the responses of reticulospinal neurons did not change by increasing the peak amplitude of tilt from 5 to 20 degrees at the fixed frequency of 0.026 Hz. This finding indicates that the system was relatively linear with respect to the amplitude of displacement. By varying the frequency of stimulation from 0.008 to 0.32 Hz at the fixed amplitude of 10 degrees, two populations of reticulospinal neurons were observed. In the first, the gain and the phase angle of response remained relatively unmodified against changes in frequencies: these positional responses were attributed to stimulation of macular receptors.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Central compensation of vestibular deficits. II. Influences of roll tilt on different-size lateral vestibular neurons after ipsilateral labyrinth deafferentation.

The activity of 168 Deiters' neurons projecting to lumbosacral segments of the spinal cord has been recorded in precollicular decerebrate cats after ipsilateral acute (aVN) or chronic vestibular neurectomy (cVN), and their response characteristics to sinusoidal stimulation of contralateral labyrinth receptors at the standard parameters (roll tilt at 0.026 Hz, 10 degrees peak displacement) have been related to cell size inferred from the conduction velocity of the corresponding axons. These findings were compared with those elicited in decerebrate cats with both vestibular nerves intact. In all experimental conditions, the higher the coefficient of variation (CV) of the vestibulospinal neurons, reflecting a more irregular unit discharge, the lower was the mean discharge rate at rest. However, the proportion of regularly discharging units (with the lowest CV) decreased after aVN but increased after cVN. The relation found in control experiments, i.e., the faster the conduction velocity of vestibulospinal axon the lower was the unit discharge at rest, was lost after aVN due to a decrease in resting discharge rate of the slow neurons. The mean discharge rate of these units, however, recovered after cVN, so that the negative correlation between resting discharge rate and axonal conduction velocity was reestablished. After aVN, the decrease in resting discharge rate of the slow vestibulospinal neurons was not associated with significant changes in gain (impulses per second per degree) of the unit responses to standard parameters of tilt, so that the sensitivity of these units (percentage change of the mean discharge rate per degree) increased; on the other hand, the resting discharge rate of the fast neurons, which remained almost unchanged after aVN, was associated with a significant increase in gain, thus leading to an average increase in response sensitivity of these units.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Neurotransmission in the human labyrinth.

Different neuroactive substances have been found in the efferent pathways of both the olivocochlear and vestibular systems. In the present study, the distribution and role of three neurotransmitters, choline acetyltransferase (ChAT), gamma aminobutyric acid (GABA), and enkephalin were investigated in the human labyrinth of 4 normal-hearing individuals. Immunohistochemical studies in human inner ear research, however, face a problem of procuring well-preserved specimens with maintained neurotransmitter antigenicity and morphology. Methods and findings are reported and discussed.

Choline O-Acetyltransferase↗

Effect of furosemide on basal lamina anionic sites in guinea pig labyrinth.

The authors studied the effects of acute furosemide administration on the basal lamina (BL) anionic sites in the stria vascularis, ampullar crista, and endolymphatic sac by using cationic polyethyleneimine (PEI). Furosemide was intravenously administered to albino guinea pigs with normal Preyer's reflexes. After 20 minutes, the bony labyrinth was removed and processed for histologic evaluation. Under a transmission electron microscope, a marked enlargement of the intercellular spaces was observed in the stria vascularis. The PEI distribution decreased significantly on the capillary BL in the stria vascularis and on the subepithelial BL in the sensory, transitional, and dark cell areas. However, no significant change was observed on the capillary BL or the subepithelial BL in the endolymphatic sac. These findings suggest that acute furosemide administration severely alters the distribution of the anionic sites in the strial capillary BL and in the subepithelial BL in the ampullar crista, but not in the capillary BL or the subepithelial BL of the endolymphatic sac.

Animals↗

Carbonic anhydrase activity in stria vascularis and dark cells in vestibular labyrinth.

Carbonic anhydrase activity was demonstrated ultracytochemically in the dark cells of the vestibular labyrinth and in the stria vascularis of the guinea pig. Reaction products were found both in the dark cells and in the stria vascularis. Localization of carbonic anhydrase was very similar between the dark cells and the intermediate cells, but the marginal cells had a different localization pattern. In both the dark cells and the intermediate cells, the reaction products were deposited in the cytoplasm, especially in the infoldings. In the marginal cells, carbonic anhydrase activity was observed on the lateral plasma membrane of the apical area and in a few apical vesicles, but was not detected in the infoldings of the deep portion. Reaction products were also observed in the intercellular spaces between the marginal cells. No reaction products were observed in the basal cells and transition cells. Carbonic anhydrase activity was observed in the cytoplasm of capillary endothelial cells and the fibrocytes of the spiral ligament. It is considered that carbonic anhydrase may play a major role in water and electrolyte transport in both the dark cells and stria vascularis.

Adenosine Triphosphatases↗

Computed tomography of the ethmoid labyrinth and adjacent structures.

The architecture of ethmoid labyrinths as well as their relationships with adjacent structures are reviewed, giving special emphasis to the anatomic variants common in this area. The study was performed on six young normal subjects who were submitted to high resolution computed tomography. Approximately 25 axial scans, parallel to the floor of the anterior cranial fossa, were performed on each subject; four to five coronal CT scans were also added. Further data were supplemented by examinations of 62 patients affected by nonneoplastic disease of the paranasal sinuses. Microsurgery is replacing classic macrosurgery in the treatment of nonneoplastic disease of the paranasal sinuses. This new trend requires a perfect preoperative delineation of the anatomy. For this purpose, the present paper contains a list of 10 questions which can be answered exhaustively by computed tomography on the basis of the data illustrated. The answers cover most requirements of sinus microsurgery.

Adult↗

Middle ear pressure and dysfunction of the labyrinth: is there a relationship?

Relationships between middle ear pressure and non-infection-related cochleovestibular dysfunction have been suggested by several authors. According to some data, vertiginous attacks can be prevented by the insertion of a ventilation tube in patients suffering from Meniere's syndrome. The aim of our study was to investigate if the incidence of eustachian tube malfunction and pathologic middle ear pressure is frequent, and if routine implantation of ventilation tubes is reasonable in ears with dysfunctions of the labyrinth, including clinical Meniere's syndrome. So, we determined in our pressure chamber all active and passive parameters of eustachian tube function in 40 patients suffering from Meniere's syndrome, sudden sensory hearing impairment (SSHI), or vestibular neuronitis. Our results disclosed no nonrandom incidence of impaired tubal function among our patients compared to healthy control subjects. Pressure equalization was sufficient in most patients suffering from clinical Meniere's syndrome, and only one patient with vestibular neuronitis presented with a patulous tube. Our results show that impairment of vestibular or cochlear function is not regularly accompanied by eustachian tube dysfunction. Furthermore, no patient reported symptoms while pressure variation was performed. We conclude that variation of middle ear pressure does not usually play a role in the genesis of Meniere's syndrome, vestibular neuronitis, or SSHI. Thus, from our data, we cannot recommend routine implantation of tympanic ventilation tubes in patients suffering from Meniere's syndrome, vestibular neuronitis, or sudden hearing loss.

Compliance↗

Pressure gradients affecting the labyrinth during hypobaric pressure. Experimental study.

Hypobaric effects on the perilymph pressure were investigated in 18 cats. The perilymph, tympanic cavity, cerebrospinal fluid, and systemic and ambient pressure changes were continuously recorded relative to the atmospheric pressure. The pressure equilibration of the eustachian tube and the cochlear aqueduct was studied, as well as the effects of blocking these channels. During ascent, the physiologic opening of the eustachian tube reduced the pressure gradients across the tympanic membrane. The patent cochlear aqueduct equilibrated perilymph pressure to cerebrospinal fluid compartment levels with a considerable pressure gradient across the oval and round windows. With the aqueduct blocked, the pressure decrease within the labyrinth and tympanic cavities was limited, resulting in large pressure gradients toward the chamber and the cerebrospinal fluid compartments, respectively. We conclude that closed cavities with limited pressure release capacities are the cause of the pressure gradients. The strain exerted by these pressure gradients is potentially harmful to the ear.

Animals↗

The unrecognized rotation of the vestibular and cochlear nerves from the labyrinth to the brain stem: its implications to surgery of the eighth cranial nerve.

The cochlear and vestibular nerves rotate 90 degrees from the inner ear to the brain stem. Most of the rotation occurs within the internal auditory canal (IAC); only minimal rotation occurs in the cerebellopontine (CP) angle. At the labyrinthine end of the IAC, the cochlear nerve--which at first lies anterior to the inferior vestibular nerve (saccular nerve)--rapidly fuses with the inferior vestibular nerve. It then rotates to become inferior as the nerves leave the porus acousticus. The cochleovestibular (C-V) cleavage plane lies in a superior-inferior direction in the lateral IAC and rotates to become anterior-posterior in the CP angle. In 25% of patients in whom no C-V cleavage plane can be seen, it is not possible to completely transect all vestibular fibers. The surgical implications are that the most complete vestibular neurectomy can be done only in the lateral IAC, the cochlear and inferior vestibular nerves, because of their intimate association, should not be separated in the mid-IAC, in order to prevent damage to the cochlear nerve, and to create a complete denervation of the vestibular labyrinth, only the posterior ampullary nerve along with the superior vestibular nerve should be transected.

Brain Stem↗

Mice lacking HSP90beta fail to develop a placental labyrinth.

The 90 kDa heat-shock proteins (HSP90s) play important roles during stress situations as general chaperones and under physiological conditions in the conformational activation of specific protein substrates. Vertebrates express two cytosolic HSP90s (HSP90alpha and HSP90beta) ubiquitously. We have mutated the Hsp90beta gene in murine embryonic stem cells and generated Hsp90beta mutant mice. Heterozygous animals were phenotypically normal. Interestingly, homozygous embryos developed normally until embryonic day 9.0/9.5. Then, although Hsp90beta is expressed ubiquitously, they exhibited phenotypic abnormalities restricted to the placenta. The mutant concepti failed to form a fetal placental labyrinth and died a day later. Fusion between the allantois and the chorionic plate occurred, allantoic blood vessels invaded the chorion, but then did not expand. Mutant trophoblast cells failed to differentiate into trilaminar labyrinthine trophoblast. Despite conspicuous similarities between HSP90alpha and HSP90beta at the molecular level, our data suggest that HSP90beta has a key role in placenta development that cannot be performed by the endogenous HSP90alpha alone. Analysis of chimeric concepti consisting of mutant embryos and tetraploid embryos or ES cells revealed that wild-type allantois was able to induce mutant trophoblast to differentiate. In contrast, trophoblast wild type at the Hsp90beta locus was unable to differentiate when in contact with mutant allantois. Therefore, the primary defect caused by the Hsp90beta mutation resided in the allantois. The allantois mesoderm is thought to induce trophoblast differentiation. Our results show that Hsp90beta is a necessary component of this induction process.

Animals↗