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[Brain stem neurons of the guinea pig that form projections into the ampullae of the anterior, lateral and posterior semicircular canals].

Brain stem neurons projecting to the ampullae of anterior, lateral and posterior semicircular canals (vestibular efferent neurons) were identified in guinea pigs using, retrograde labelling with horseradish peroxidase. Two groups of such neurons located bilaterally dorsal and ventral to the facial nerve trajectory were classified. A dorsal group contained vestibular efferent neurons to all three canals; these units were located at all the levels of the subependymal granular layer of the floor of the 4th ventricle lateral to the facial nerve genu and abducens nerve nucleus. Vestibular efferent neurons of the ventral group were distributed within different parts of parvocellular and rostral part of the caudal pontine reticular nucleus. Heterogeneity of organization of the vestibular efferent system of semicircular canal ampullae according to cell location and their morphological characteristics are discussed.

Animals↗

Ultrastructural changes in contralateral superior vestibulo-ocular neurons one year after vestibular neurectomy in the cat.

Twenty contralateral superior vestibulo-ocular neurons (SVON) from 3 cats were studied morphologically one year after a right vestibular neurectomy. Eighteen SVON contained a smooth or slightly crenated nuclear membrane, a 63% loss of synaptic profiles (SP) and a 22% decrease in size compared to control SVON. Two cells contained nuclear membrane invaginations, a 40% loss of SP and a 31% size decrease compared to control SVON. The volume fractions of rough endoplasmic reticulum and ribosomes were decreased in these two cell groups but no change was noted in Golgi apparatus and mitochondria. These contralateral SVON reached a size, innervation density and content of organelles similar to ipsilateral SVON at one year following vestibular neurectomy.

Animals↗

[Postvibration changes in the spontaneous activity of neurons in the medial vestibular nucleus].

The method of computer analyses was used for the research of the spectral changes of spontaneous neuronal activity of the medial vestibular nucleus ander vibration action (5, 10 and 15 daily). On the basis of neurons activity analyses it is possible to conclude that the majority of investigated units of flow and instability figured on different levels. The findings are discussed in respect to special points of functional meaning.

Action Potentials↗

Age related changes in neuron number in the mouse lateral vestibular nucleus.

The number of large neurons in the lateral vestibular nucleus of the mouse brain decreases in number after 25 months of age, from 488 at 25 months to 298 at 31 months. The number of small neurons in the nucleus remains constant up to 31 months of age. Large neurons accumulate lipofuscin from 25 months and their mean nuclear diameter increases significantly between 25 and 28 months of age. Small neurons contain very little lipofuscin even at 31 months of age and their mean nuclear diameter remains constant between 6 and 31 months. The difference in response of the two types of neurons to ageing may be due to their connections. Large neurons project to spinal motor neurons which decline in number with age and they receive projections from Purkinje cells in the anterior lobe of the cerebellum which also decline in number with age. Small neurons mainly project to the oculogyric nuclei in at least one of which (the abducens) there is no loss of neurons up to 31 months of age.

Aging↗

Modulation of neuronal activity by EGCG.

This study aims to investigate whether (-)-epigallocatechin-3-gallate (EGCG) affects neuronal activity of acutely isolated rat medial vestibular nuclear neurons in whole-cell configuration patch-clamp experiments. EGCG (0.5 and 1 muM) lowered the spontaneous firing rate and hyperpolarized the membrane potential of medial vestibular nuclear neurons. However, it did not change the amplitude of afterhyperpolarization or the spike width of the action potential. A second application of EGCG with the same concentration elicited lesser responses. These results suggest that EGCG decreases neuronal activity by affecting potassium currents which are responsible for membrane potentials.

Action Potentials↗

Properties of superior vestibular nucleus flocculus target neurons in the squirrel monkey. I. General properties in comparison with flocculus projecting neurons.

1. Using single-unit recording and microstimulation methods, a group of flocculus target neurons (FTNs) were identified in the superior vestibular nucleus (SVN) and were studied using visual-vestibular interaction paradigms in alert squirrel monkeys. The response properties of these FTNs were characterized and compared with those of flocculus projecting neurons (FPNs). 2. FTNs were monosynaptically inhibited by single-pulse flocculus stimulation. The mean inhibition latency was 1.0 +/- 0.57 (SD) ms (n = 40) and the mean inhibition period was 6.7 +/- 2.69 ms. FTNs were also monosynaptically activated by VIIIth nerve stimulation. The mean response latency was 1.10 +/- 0.25 ms (n = 12). This is about the same as that of the FPNs (1.14 +/- 0.16 ms, n = 17). 3. The most characteristic response property of the FTNs is their firing rate modulation during visual following eye movements induced by sinusoidal rotation of an optokinetic drum at 0.5 Hz. This modulation was mainly related to eye velocity and was therefore termed a visual following eye velocity signal. The average eye velocity gain for all FTNs is 0.79 spikes.s-1.deg-1.s-1. In contrast, the responses of FPNs were not modulated under the same conditions. 4. Even though FTNs are inhibited by the flocculus, they have a relatively higher mean firing rate (124 +/- 23 spikes/s, n = 45) than FPNs (66 +/- 28 spikes/s, n = 42). The underlying mechanism may be related to commissural facilitation of FTNs and commissural inhibition of FPNs. 5. Thirty FTNs were identified as upward eye velocity FTNs because their firing rate increased for upward eye velocity during a visual following eye movement. The mean eye velocity sensitivity was 1.09 spikes.s-1.deg-1.s-1. Most of these cells also modulated during vestibuloocular reflex (VOR) in the dark, with firing rate increasing for downward head velocity. During VOR suppression the firing rate either did not modulate or modulated in phase with head or drum velocity with a smaller amplitude in comparison with the response during visual following. For all cells (with 1 exception) the response during a visual following eye movement can be approximately predicted by a linear vectorial subtraction of the response during VOR suppression and the response during VOR in the dark [modulation response vector of FTNs during visual following of the optokinetic stimulus (OKR) approximately modulation response vector of FTNs during VOR suppression-modulation response vector of FTNs during VOR in the dark].(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Timing and regulation of trkB and BDNF mRNA expression in placode-derived sensory neurons and their targets.

The sensory neurons of the vestibular and nodose ganglia of the chicken embryo have nearby and distant targets, respectively. In vitro studies have shown that these neurons survive independently of neurotrophins when their axons are growing to their targets and become dependent on brain-derived neurotrophic factor (BDNF) for survival when their axons reach the vicinity of their targets. Although the timing of BDNF dependence is principally controlled by an intrinsic timing mechanism in the neurons, the onset of dependence can be accelerated by BDNF exposure toward the end of the phase of neurotrophin independence. We have used quantitative reverse transcription/polymerase chain reaction to study the expression of transcripts coding for BDNF and the catalytic isoform of its receptor tyrosine kinase, TrkB, in these neurons and their targets at different stages of development. We show that the peripheral and central target tissues of these neurons express BDNF mRNA prior to the arrival of sensory axons. Vestibular neurons express trkB mRNA before nodose neurons, which accords with the earlier response of vestibular neurons to BDNF. In culture, early nodose neurons start expressing trkB mRNA after 36 h incubation, which is 36 h before these neurons become dependent on BDNF for survival. Although BDNF does not affect the timing and level of trkB mRNA expression during the first 48 h in vitro, it increases the level of trkB mRNA after this time. The timing of BDNF-induced elevation of trkB mRNA correlates with the period during which BDNF exposure accelerates the onset of BDNF dependence in nodose neurons. These results suggest that the timing of BDNF dependence in developing sensory neurons is due in part to expression of catalytic TrkB and demonstrate that a BDNF autocrine loop is not required for the survival of sensory neurons during the earliest stages of their development.

Animals↗

Vestibular and cochlear efferent neurons in the monkey identified by immunocytochemical methods.

Attempts were made to identify vestibular (VEN) and cochlear (CEN) efferent neurons in the squirrel monkey using retrograde transport of horseradish peroxidase (HRP) and immunocytochemical methods. HRP implants in the ampulla of the lateral semicircular duct retrogradely labeled cells of VEN bilaterally and some cells of CEN. VEN located lateral to the rostral part of the abducens nucleus formed a compact collection of cells, all of which were immunoreactive only to antisera for choline acetyltransferase (ChAT). CEN, identified by immunoreactivity to ChAT were located at the hilus of the lateral superior olive (LSO), along the lateral border of the LSO and sparsely near lateral parts of the ventral trapezoid nucleus (VTN). A small number of cells and fibers near the border of the VTN and lateral to the LSO were immunoreactive for leucine enkephalin (L-ENK). Fibers immunoreactive for L-ENK also were identified in the hilus of the LSO. No cells of the superior olivary complex were immunoreactive for antisera to ChAT, L-ENK, substance P, gamma-aminobutyric acid or glutamic acid decarboxylase. Cells of VEN and CEN can be identified by their immunoreactivity to ChAT, and some cells and fibers of CEN also contain L-ENK.

Animals↗

Multiple actions of neurturin correlate with spatiotemporal patterns of Ret expression in developing chick cranial ganglion neurons.

The neurotrophic effects of neurturin (NRTN) on chick cranial ganglia were evaluated at various embryonic stages in vitro and related to its receptor expression. NRTN promoted the outgrowth and survival of ciliary ganglion neurons at early embryonic (E) stages (E6-E12), trigeminal ganglion neurons at midstages (E9-E16), and vestibular ganglion neurons at late stages (E12-E16). NRTN had no positive effects on cochlear ganglion neurons throughout development. In accordance with the time and order of onset in NRTN responsiveness, Ret protein was first detected in ciliary ganglia at E6, subsequently in trigeminal ganglia at E9, and in vestibular ganglia at E12. Ret was absent in E16 ciliary ganglia as well as in cochlear ganglia at all developmental stages that were tested. Exogenous application of retinoic acid induced NRTN responsiveness and Ret protein expression from E9 vestibular ganglion neurons, suggesting that retinoic acid can regulate Ret protein expression in peripheral sensory neurons in vitro. Ret was confined to the neuron cell body, whereas GFRalpha was localized predominantly in peripheral and central neurite processes. No noticeable change in GFRalpha expression was seen in any cranial ganglia throughout the developmental stages that were tested (E6-E16). These results demonstrate that NRTN exerts neurotrophic effects on different cranial ganglia at different developmental stages and that the onset and offset of NRTN responsiveness are regulated mainly by the spatiotemporal patterns of Ret, but not of GFRalpha receptors. The results also substantiate the recently emerging view that NRTN may be an essential target-derived neurotrophic factor for parasympathetic neurons during development.

Animals↗

Spatio-temporal convergence (STC) in otolith neurons.

It has been recently demonstrated that some primary otolith afferents and most otolith-related vestibular nuclei neurons encode two spatial dimensions that can be described by two vectors in temporal and spatial quadrature. These cells are called broadly-tuned neurons. They are characterized by a non-zero tuning ratio which is defined as the ratio of the minimum over the maximum sensitivity of the neuron. Broadly-tuned neurons exhibit response gains that do not vary according to the cosine of the angle between the stimulus direction and the cell's maximum sensitivity vector and response phase values that depend on stimulus orientation. These responses were observed during stimulation with pure linear acceleration and can be explained by spatio-temporal convergence (STC) of primary otolith afferents and/or otolith hair cells. Simulations of STC of the inputs to primary otolith afferents and vestibular nuclei neurons have revealed interesting characteristics: First, in the case of two narrowly-tuned input signals, the largest tuning ratio is achieved when the input signals are of equal gain. The smaller the phase difference between the input vectors, the larger the orientation differences that are required to produce a certain tuning ratio. Orientation and temporal phase differences of 30-40 degrees create tuning ratios of approximately 0.10-0.15 in target neurons. Second, in the case of multiple input signals, the larger the number of converging inputs, the smaller the tuning ratio of the target neuron. The tuning ratio depends on the number of input units, as long as there are not more than about 10. For more than 10-20 input vectors, the tuning ratio becomes almost independent of the number of inputs. Further, if the inputs comprise two populations (with different gain and phase values at a given stimulus frequency), the largest tuning ratio is obtained when the larger population has a smaller gain. These findings are discussed in the context of known anatomical and physiological characteristics of innervation patterns of primary otolith afferents and their possible convergence onto vestibular nuclei neurons.

Hearing↗

Ventral respiratory group bulbospinal inspiratory neurons participate in vestibular-respiratory reflexes.

1. The vestibular system responds to accelerations of the head and produces reflex responses that serve a variety of compensatory functions. The neuronal circuitry that mediates vestibulo-respiratory reflexes is largely unknown. The purpose of the present study was to investigate the possible role of bulbospinal inspiratory neurons located in the para-ambigual region of the ventral respiratory group (VRG) in mediating these reflexes. Experiments were carried out in cats that were decerebrated, paralyzed, and artificially ventilated. 2. Activation of the vestibular nerve by electrical stimulation produced prominent bilateral reflex responses recorded from the phrenic nerve, which supplies the diaphragm. The responses could be complex and consisted of a decrease and/or increase in nerve discharge. 3. Extracellular recordings were made from 35 VRG inspiratory neurons that were antidromically activated from the upper cervical spinal cord. Almost one-half of these neurons (15/35, 43%) responded to vestibular stimulation. The neuronal response patterns were consistent with VRG inspiratory neurons contributing to the vestibular reflex response simultaneously recorded from the phrenic nerve. 4. The present results indicate that approximately one-half of VRG bulbospinal inspiratory neurons contribute to vestibulo-respiratory reflexes. These findings are in contrast to our recent neuroanatomic and electrophysiological studies which revealed a paucity of vestibular inputs to the dorsal respiratory group (DRG) located in the ventrolateral nucleus of the solitary tract. Thus there appears to be a difference between inspiratory neurons in the DRG and VRG in regard to participating in vestibulo-respiratory reflexes.

Animals↗

Response properties of neurons in posterior parietal cortex of monkey during visual-vestibular stimulation. I. Visual tracking neurons.

Extracellular recordings were obtained from 163 visual tracking neurons in area 7a or PG (24) of alert monkeys. The firing patterns were observed during movements of the chair in which the monkey was seated with its head fixed and of a visual target that the monkey was trained to fixate continuously. Horizontal visual tracking neurons were classified into three groups, A, B, and C, on the basis of the following two discharge characteristics: directional preference for visual tracking and response to horizontal sinusoidal oscillation of the chair in the dark. Those neurons that did not respond to chair oscillations in the dark were classified as type A (26/53). Of the remainder, those that responded with the same directional preference as during visual tracking were classified as type B (19/53), and those that showed the opposite directional preference were classified as type C (8/53). When the target and the chair were oscillated together and the monkey canceled the vestibuloocular reflex (VOR) (combined eye and head tracking), most of the visual tracking neurons (types A and B, 32/38) continued to respond in the same way as during visual tracking when the chair was stationary. Type C neurons showed only weak responses. When the monkey fixated an earth-fixed target while the chair was oscillated sinusoidally (VOR target task), responses of the types A and B neurons were much smaller than during visual tracking, while type C neurons were clearly modulated. The results suggest that visual tracking neurons receive information concerning the smooth-pursuit command during combined eye and head (gaze) movements; some also receive vestibular information in addition to the pursuit command information.

Animals↗

11Beta-hydroxysteroid dehydrogenase type 1 activity in medial vestibular nucleus and cerebellum after unilateral vestibular deafferentation in the rat.

In the early stages of vestibular compensation (VC) (the behavioural recovery that follows unilateral vestibular deafferentation), neurons in the medial vestibular nucleus (MVN) on the lesioned side develop a sustained up-regulation of their intrinsic excitability. This plasticity is dependent on the activation of glucocorticoid receptors, which presumably occurs during the acute stress response that accompanies the vestibular deafferentation symptoms. Recent studies have established that the access of glucocorticoids to their intracellular receptors in brain is potently modulated by 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1), which catalyses the generation of active glucocorticoids from their inert 11-keto forms. In this study, we investigated the presence of 11beta-HSD1 bioactivity, and possible changes in activity in the early stage after vestibular deafferentation, in the cerebellar nodulus and uvula, the flocculus/paraflocculus (F/PF) complex and the MVN of the rat. 11beta-HSD1 activity was found in each of these brain areas, with especially high levels of activity in the F/PF complex. No differences were found in the level of 11beta-HSD1 activity in these brain areas between control rats, sham-operated rats and rats that underwent VC for 4 h after unilateral vestibular deafferentation. These findings demonstrate 11beta-HSD1 bioactivity in the MVN and vestibulocerebellum, but exclude the possibility that changes in 11beta-HSD1 activity occur in the early period after deafferentation, over the time when changes in MVN neuronal properties take place.

11-beta-Hydroxysteroid Dehydrogenase Type 1↗

Optical recording of membrane potential in dissociated mouse vestibular ganglion cells using a voltage-sensitive dye.

We investigated membrane electrophysiological features of dissociated vestibular ganglion neurons, using a voltage-sensitive dye and a multiple site optical imaging system. The neuronal nature of the cultured vestibular ganglion cells was confirmed by positive staining with the anti-neurofilament 200 kDa antibody, using immunocytochemical methods. Optical absorption of the dye which binds to the external surface of neuron membranes increased while the cells were depolarized during perfusion with 150 mM potassium solution. The relative ratio (deltaI/I) of optical absorption change was 0.23 +/- 0.08% (means +/- S.D., n = 16). These optical responses were wavelength dependent, therefore, the optical response apparently originated from the voltage-sensitive dye. Under our experimental conditions, photodynamic damage and pharmacological effects of the dye were either absent or insignificant. We therefore concluded that optical recording is a new, practical and non-invasive method to simultaneously monitor changes in membrane potential from cultured vestibular ganglion cells. Optical recording is expected to provide further insight into mechanisms of information processing by vestibular ganglion neurons.

Absorption↗

Electrophysiological evidence for cholinoceptive neurons in the medial vestibular nucleus: studies on rat brain stem in vitro.

Electrophysiological studies were performed to determine whether or not cholinoceptive neurons are present in the rat medial vestibular nucleus (MVN) using brainstem slice preparations. Fifty-three MVN neurons, whose activities were extracellularly recorded, fired spikes spontaneously and regularly with an interspike interval of 180 +/- 27 ms (mean +/- S.E.M.) and a coefficient of variation of 0.11 +/- 0.02. Intracellularly recorded neurons also exhibited similar spontaneous and regular generation of action potentials. Carbachol dose-dependently increased the spontaneous firing, although the firing rate was decreased in a few neurons. The addition of atropine reduced the firing rate, and dose-dependently attenuated the carbachol-induced excitation of the neurons. In a low Ca2+ and high Mg2+ medium, carbachol also increased the firing rate. These results indicate that the MVN contains neurons with spontaneous and regular firing, and that the excitability of these neurons is regulated by a cholinergic muscarinic mechanism.

Animals↗

Development of inner ear afferent connections: forming primary neurons and connecting them to the developing sensory epithelia.

The molecular and cellular origin of the primary neurons of the inner ear, the vestibular and spiral neurons, is reviewed including how they connect to the specific sensory epithelia and what the molecular nature of their survival is. Primary neurons of the ear depend on a single basic Helix-Loop-Helix (bHLH) protein for their formation, neurogenin 1 (ngn1). An immediate downstream gene is the bHLH gene neuronal differentiation (NeuroD). Targeted null mutations of ngn1 results in absence of primary neuron formation; targeted null mutation of NeuroD results in loss of almost all spiral and many vestibular neurons. NeuroD and a later expressed gene, Brn3a, play a role in pathfinding to and within sensory epithelia. The molecular nature of this pathfinding property is unknown. Reduction of hair cells in ngn1 null mutations suggests a clonal relationship with primary neurons. This relationship may play some role in specifying the identity of hair cells and the primary neurons that connect with them. Primary neuron neurites growth to sensory epithelia is initially independent of trophic factors released from developing sensory epithelia, but becomes rapidly dependent on those factors. Null mutations of specific neurotrophic factors lose distinct primary neuron populations which undergo rapid embryonic cell death.

Animals↗

Isolated directional preponderance of caloric nystagmus: I. Clinical significance.

OBJECTIVES: To determine the clinical significance of an isolated directional preponderance (DP) on bithermal caloric testing. An isolated caloric DP was defined as a DP, calculated according to the standard Jongkees formula, of > or = 40%, with a spontaneous nystagmus (SN) in darkness of < or = 2 degrees/s and a canal paresis (unilateral weakness) of < or = 25%. STUDY DESIGN: A retrospective analysis of all 15,542 bithermal caloric tests performed in the authors' department in the previous 10 years to identify all tests with an isolated DP of > or = 40%. This was followed by a review of the clinical data on the 144 patients identified with such a result and then by a telephone or postal follow-up study of these patients. The study group eventually comprised 114 patients; these were patients in whom a clinical diagnosis could be made at the time the caloric test was done, or who responded to requests for follow-up information. The 34 patients in whom a clinical diagnosis could not be made at the time of the caloric test, and who did not respond to requests for follow-up information, were excluded. STUDY SETTING: A balance disorders clinic in a tertiary referral hospital. INTERVENTION: All patients underwent standard bithermal caloric testing. Some of the patients also underwent rotational testing. OUTCOME MEASURES: A clinical diagnosis for the cause of the isolated DP, made either at the time of the caloric test or on the basis of information supplied at follow-up by the patient or by the referring physician. RESULTS: Of 114 patients, 39 had benign paroxysmal positioning vertigo, 14 had Ménière's disease, and 5 had migrainous vertigo. Five patients had central nervous system (CNS) disorders, and this was clinically apparent at the time of the caloric test in 4, so that only 1 patient with an isolated DP developed evidence of a CNS disorder after the caloric test was done. In the other 54 patients, no definite diagnosis could be made, but 41 of these 54 were either completely well or much better at follow-up. CONCLUSIONS: An isolated DP on caloric testing is usually a transient, benign disorder. About half the patients with an isolated DP have either Ménière's disease or benign paroxysmal positioning vertigo; in most of the other half, no definite diagnosis is made but most of these patients will do well. Only approximately 5% have a CNS lesion and in almost all this is apparent at the time the caloric test is done. In a relapsing-remitting peripheral vestibular disorder such as benign paroxysmal positioning vertigo or Ménière's disease, the mechanism of an isolated DP could be enhanced dynamic gain of ipsilesional medial vestibular nucleus neurons, perhaps as a result of intermittent hyperfunction of primary semicircular canal vestibular afferents. The authors postulate that an isolated DP reflects a gain asymmetry between neurons in the medial vestibular nucleus on either side, caused either by increased sensitivity on one side or by reduced sensitivity on the other, perhaps as an adaptive change in response to abnormal input. In an accompanying article, the authors implement a realistic neural network model in which it is possible to simulate an isolated DP by adjusting the dynamic sensitivity of type 1 medial vestibular nucleus neurons on one side or of type 2 medial vestibular nucleus neurons on the other.

Caloric Tests↗

Immunocytochemical localization of mitochondrial and cytosolic aspartate aminotransferase isozymes in the vestibular end-organs of rats.

The localization of mitochondrial (m-) and cytosolic (c-) aspartate aminotransferase (AAT) was examined in the vestibular ganglion neurons and sensory cells in the vestibular end-organs of rats by an indirect immunohistochemical method using antibodies specific for m- and c-AAT. Neurons in the vestibular ganglion were stained by both m- and c-AAT antibodies, but the vestibular sensory cells exhibited only m-AAT-like immunoreactivity and were not labeled by c-AAT. These findings suggested that aspartate is a neurotransmitter in the hair cells of the vestibular end-organs.

Animals↗