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PubMed2004

Effects of bilateral vestibular nucleus lesions on cardiovascular regulation in conscious cats.

The vestibular system participates in cardiovascular regulation during postural changes. In prior studies (Holmes MJ, Cotter LA, Arendt HE, Cas SP, and Yates BJ. Brain Res 938: 62-72, 2002, and Jian BJ, Cotter LA, Emanuel BA, Cass SP, and Yates BJ. J Appl Physiol 86: 1552-1560, 1999), transection of the vestibular nerves resulted in instability in blood pressure during nose-up body tilts, particularly when no visual information reflecting body position in space was available. However, recovery of orthostatic tolerance occurred within 1 wk, presumably because the vestibular nuclei integrate a variety of sensory inputs reflecting body location. The present study tested the hypothesis that lesions of the vestibular nuclei result in persistent cardiovascular deficits during orthostatic challenges. Blood pressure and heart rate were monitored in five conscious cats during nose-up tilts of varying amplitude, both before and after chemical lesions of the vestibular nuclei. Before lesions, blood pressure remained relatively stable during tilts. In all animals, the blood pressure responses to nose-up tilts were altered by damage to the medial and inferior vestibular nuclei; these effects were noted both when animals were tested in the presence and absence of visual feedback. In four of the five animals, the lesions also resulted in augmented heart rate increases from baseline values during 60 degrees nose-up tilts. These effects persisted for longer than 1 wk, but they gradually resolved over time, except in the animal with the worst deficits. These observations suggest that recovery of compensatory cardiovascular responses after loss of vestibular inputs is accomplished at least in part through plastic changes in the vestibular nuclei and the enhancement of the ability of vestibular nucleus neurons to discriminate body position in space by employing nonlabyrinthine signals.

Adaptation, Physiological↗
PubMed2003

Differential impact of hypergravity on maturating innervation in vestibular epithelia during rat development.

Over the past decades, the new opportunity of space flights has revealed the importance of gravity as a mechanical constraint for terrestrial organisms as well as its influence on the somatosensory system. The lack of gravitational reference in orbital flight induces changes in equilibrium, with major modifications involving neuromorphological and physiological adaptations. However, few data have illustrated the putative effect of gravity on sensory vestibular epithelial development. We asked if gravity, the primary stimulus of utricles could act as an epigenetic factor. As sensorial deprivation linked to weightlessness is technically difficult, we used a ground-based centrifuge to increase the gravitational vector, in order to hyperstimulate the vestibule. In this study, 3 days after mating, pregnant females were submitted to hypergravity, 2 g (HG). Their embryos were raised, born and postnatally developed under HG. The establishment of connections between primary vestibular afferent neurons and hair cells in the utricle of these young rats was followed from birth to postnatal day 6 (PN6) and compared to embryos developed in normogravity (NG): Immunocytochemistry for neurofilaments and microvesicles revealed the differential effects of gravity on the late neuritogenic and synaptogenic processes in utricles. Taking type I hair cell innervation as a criterion of maturation, we found that primary afferent fibres reached the vestibular epithelium and enveloped hair cells in the same way, both under NG and HG. Thus, this phenomenon of leading growth cones to their epithelial target appears to be dependent on intrinsic genetic properties and not on an external stimulus. In contrast, the maturation of connection processes between type 1 hair cells and the afferent calyx, concerning specifically the microvesicles at their apex, was delayed under HG. Therefore, gravity appears to be an epigenetic factor influencing the late maturation of utricles. These differential effects of altered gravity on the development of the vestibular epithelium are discussed.

Animals↗
PubMed1993

Vestibular pathology of totally deaf ears.

The temporal bone vestibular pathologies of 23 totally deaf ears (16 patients) were studied. Abnormal findings in the saccule were seen more often than in the other vestibular sensory organs. Abnormal findings in the vestibular ganglion cells were found in 7 ears. There were fewer ears with main damage in the hair cells than with main damage in the nerves.

Adolescent↗
PubMed1996

Optokinetic and vestibulo-ocular reflex adjustment by GABA antagonists.

We determined if high and low doses of anti-GABAergic drugs have opposite effects on the visuo-vestibular activity in pigmented rats and examined a possible correlation with the level of GABA in the related structures. First, the horizontal optokinetic and vestibulo-ocular reflexes of most animals were depressed by high doses of anti-GABAergic drugs (10(-3) M purified picrotoxin or 10(-6) M picrotoxin in unpurified vegetal extract). Simultaneously, a drop in GABA level in the cerebellum and posterior brainstem was detected. Second, after a subsequent injection (1 ml) of the diluted extract (10(-13) M picrotoxin), the reflexes returned to normal despite the fact that no correlation with the GABA level was found. These results demonstrate that small doses of anti-GABAergic drugs reverse the depressive effect created by large doses of these drugs on the oculomotor system, and even adjust the reflexes to the stimulation. This adjustment, without correlation with the GABA level, suggest a powerful effect of very low dose of the drug to modulate either the activity of the cerebellar inhibiting input or of the vestibular nuclei neurons or to trigger the adaptation by other neurotransmitter systems involved in the performances of the reflexes.

Animals↗
PubMed1975

[Reactions of human neck muscle-fibers to vestibular stimulation (author's transl)].

In healthy human subjects activity from single fibers of the splenius-capitis muscle was recorded by means of a microelectrode. Two types of muscle fibers could be distinguished according to their reaction on vestibular stimulation. The first type reacted only to stimuli (angular acceleration) exceeding 10 degrees per sec2. These units showed no resting activity. The second type had a resting activity between 20 to 40 impulses per second. Their reactions under vestibular stimulation resembled that of primary afferent neurones of the vestibular nerve of other vertebrates. The functional meaning of these findings is discussed.

Animals↗
PubMed1975

Neuronal activity in the lateral vestibular nucleus of the cat. V. Topographical distribution of inhibitory effects mediated by the spino-olivocerebellar pathway.

The spatial distribution of inhibitory effects mediated by spinoolivocerebellar pathways and evoked by stimulation of the FRA was studied in Deiters' nucleus by intracellular recordings and extracellular measurements of positive field potentials. At a geven recording site individual nerves greatly varied in their effectiveness: Q and Saph, Tib and FDL were usually the most effective, while GS had very little effect. When comparing several recording sites, various patterns of dominating and nondominating nerves were found, resulting in a somewhat patchy distribution of responses. The results were supported by intracellular recordings, which showed that CF-mediated IPSPs can be evoked from a limited number of nerves only. The findings show that a discriminative pattern exists in the FRA-evoked spino-olivocerebellar-mediated inhibition. In addition, Deiters neurones were found in which the inhibition was evoked from a large number of fore- and hindlimb nerves. Such a generalized inhibitory pattern may be involved in interlimb coordination during locomotion.

Afferent Pathways↗
PubMed2003

BDNF gene replacement reveals multiple mechanisms for establishing neurotrophin specificity during sensory nervous system development.

Neurotrophins have multiple functions during peripheral nervous system development such as controlling neuronal survival, target innervation and synaptogenesis. Neurotrophin specificity has been attributed to the selective expression of the Trk tyrosine kinase receptors in different neuronal subpopulations. However, despite overlapping expression of TrkB and TrkC in many sensory ganglia, brain-derived neurotrophic factor (BDNF) and neurotrophin 3 (NT3) null mutant mice display selective losses in neuronal subpopulations. In the present study we have replaced the coding part of the BDNF gene in mice with that of NT3 (BDNF(NT3/NT3)) to analyse the specificity and selective roles of BDNF and NT3 during development. Analysis of BDNF(NT3/NT3) mice showed striking differences in the ability of NT3 to promote survival, short-range innervation and synaptogenesis in different sensory systems. In the cochlea, specificity is achieved by a tightly controlled spatial and temporal ligand expression. In the vestibular system TrkB or TrkC activation is sufficient to promote vestibular ganglion neuron survival, while TrkB activation is required to promote proper innervation and synaptogenesis. In the gustatory system, NT3 is unable to replace the actions of BDNF possibly because of a temporally selective expression of TrkB in taste neurons. We conclude that there is no general mechanism by which neurotrophin specificity is attained and that specificity is achieved by (i) a tightly controlled spatial and temporal expression of ligands, (ii) different Trk receptors playing distinct roles within the same neuronal subpopulation, or (iii) selective receptor expression in sensory neuron subpopulations.

Animals↗
PubMed1975

Vestibular nystagmus and teleost oculomotor neurons: functions of electrotonic coupling and dendritic impulse initiation.

1. Nystagmus in the horizontal plane is evoked in fish by mechanical stimulation of the ampulla of the horizontal semicircular canal or by electrical stimulation of the nerve from this canal. The movements are conjugate and the slow phase is away from the side of stimulation. 2. Medial rectus motoneurons were recorded from intracellularly, during nystagmus. During the slow phase (induced by ipsilateral stimulation), impulses arise abruptly from the base line and appear to arise at a distance from the cell body. During the fast phase (evoked by contralateral stimulation), impulses appear to arise from large PSPs that must be generated at or near the cell body. 3. In the curarized fish, stimulation of the nerve from the contralateral horizontal canal evokes spikes that arise from large EPSPs and that are blocked relatively easily by hyperpolarizing currents. Stimulation of the nerve from the ipsilateral horizontal canal evokes spikes that arise abruptly from the base line and that are much more difficult to block by hyperpolarizing currents. Little if any underlying PSP is observed when these impulses are delayed or blocked. Thus impulses evoked by stimulation of contralateral and ipsilateral side are initiated near to and far from the cell soma, respectively. 4. If impulses evoked by contralateral stimulation fail to excite the cell body due to injury, antidromic spikes are not occluded. Thus contralateral stimulation initiates impulses in the dendrites. 5. Cell bodies of neighboring motoneurons are coupled electrotonically, and graded antidromic stimulation evokes graded depolarizing potentials which result from electrotonic spread of spike activity from adjacent neurons. These depolarizing potentials are adequate to excite the cells in the presence of a background EPSP evoked by contralateral canal stimulation. In this manner coupling tends to synchronize cells during the fast phase of the nystagmus. 6. Antidromic responses of neighboring cells fail to interact with dendritic inputs to a particular cell, although indirect evidence indicates antidromic spikes invade the impulse-initiating regions in the dendrites. Thus coupling between dendrites is negligible and dendritic inputs can mediate the smoothly graded movements of the slow nystagmic phase. Coupling between somata is too weak to cause significant interaction between dendritically evoked impulses (unless the cell bodies are depolarized by EPSPs). 7. Rhythmic firing can be recorded in a single presynaptic fiber corresponding to either the slow or the fast phase of nystagmus, but not to both. Oculomotor neurons appear to be "relay cells" that, during the fast phase of the nystagmus receive a synchronized synaptic input which is initiated in a higher level command nucleus.

Animals↗
PubMed1985

Neuronal mechanisms of the interaction of Deiters' nucleus with some brainstem structures.

The effects of stimulation of the interstitial nucleus of Ramón y Cajal, as well as the nucleus of Darkschewitsch, inferior olive and nucleus reticularis tegmenti pontis on the neuronal activity of the lateral vestibular nucleus of Deiters were studied by means of an intracellular recording technique. Stimulation of these structures is shown to lead to antidromic and orthodromic activation of Deiters' neurons. Collaterals of vestibulospinal neurons entering these structures are revealed electrophysiologically. It was shown that stimulation of the rostral part of the inferior olive evoked in Deiters' neurons predominantly antidromic responses, whereas stimulation of the caudal part of the inferior olive leads mostly to synaptic activation. Stimulation of Ramón y Cajal's and Darkschewitsch's nuclei evokes mono- and/or polysynaptic excitatory and inhibitory postsynaptic potentials in Deiters' neurons. Mono-, oligo- and/or polysynaptic inhibitory postsynaptic potentials were also evoked by stimulation of nucleus reticularis tegmenti pontis, as well as the rostral and particularly, caudal parts of the inferior olive. Stimulation of the caudal part of the inferior olive evoked mono-, oligo- and/or polysynaptic excitatory postsynaptic potentials in Deiters' neurons. Convergence of influences from the stimulated structures on the vestibular neurons under study was shown. A topical correlation between Deiters' nucleus and the brainstem nuclei mentioned above was found. The presence of inhibitory and excitatory interaction of these structures with Deiters' nucleus was established.

Animals↗
PubMedDate not supplied

The frog as a unique vertebrate model for studying the rhombomeric organization of functionally identified hindbrain neurons.

The segmental organization of cranial nerve efferent, vestibular, and precerebellar neurons of larval ranid frogs is essentially retained in adult frogs, indicating the absence of any substantial postembryonic longitudinal migration of hindbrain neurons in this group. Comparison of the rhombomeric organization of vestibulomotor and branchiomotor pathways across different species suggests that the frog hindbrain blueprint is common to most vertebrates. The unique segmental stability seen in frogs can be used to create a quantitative stereotactic map of the adult brain that mirrors the embryonic and larval rhombomeric framework. Such a map allows the large number of physiologically identified hindbrain neurons in adult frogs to be linked with their underlying genetic specification. Transgenic reporters and antisense knockdown of gene activities suspected of having necessary functions in patterning neurons within specific rhombomeres may allow direct testing of the proposed map.

Animals↗
PubMed2003

Cellular localization of TWIK-1, a two-pore-domain potassium channel in the rodent inner ear.

K(+) channels in the inner ear regulate the secretion and homeostasis of K(+), i.e. the flux of K(+) ions required to ensure good mechanosensory transduction. We studied the expression and cellular localization of TWIK-1 and TWIK-2, two-pore-domain K(+) channels responsible for background K(+) currents. Reverse transcription-polymerase chain reaction showed that TWIK-1 mRNA is present in the vestibular end organs, vestibular ganglion and cochlea. In contrast, the TWIK-2 mRNA was not detected in the inner ear. Immunocytochemical experiments using confocal microscopy showed that TWIK-1 is specifically localized in 'non-sensory' cells of the inner ear, in the dark cells of the vestibule and in the strial marginal cells of the cochlea. All of these cell types secrete and regulate the K(+) endolymph production and homeostasis. The labeling was strictly limited to the apical membranes of these cells. TWIK-1 was also detected in the cytoplasm of the large neurons of vestibular ganglion and their fibers. The finding that TWIK-1 is specifically distributed in certain areas of the inner ear suggests that this type of K(+) channel plays a role in the regulation of K(+) homeostasis in dark cells and in strial marginal cells. This role has yet to be identified.

Aging↗
PubMedDate not supplied

[Vestibular nerves and nuclei throughout history].

Throughout the evolution of the concepts concerning the peripheral nerves, different ideas have dominated at different moments in history. The studies and demonstrations conducted in an attempt to further our knowledge of our own constitution and working at the same time enabled us to gain a better understanding of the make-up and specific functioning of the vestibular nerves, together with their central connecting elements in the brainstem: the vestibular nuclei. It may be that the first references to vestibular nerves are now lost in time, yet the Ancient Greeks already attempted to understand their functional nature by carrying out studies essentially focused on neuroanatomical aspects, but heavily influenced by philosophical concepts. It was not until the 18th century that researchers came to understand that there were differences between the vestibular nerve and the cochlear nerve --until then they were believed to be one single nerve. Another century went by before attempts were made to clarify the role it plays in balance and not in hearing. The differences between the distinct vestibular nuclei situated between the medulla oblongata and the pons were established in the 19th and 20th centuries when a number of authors, backed by previous microscopic studies, contributed to clarifying the fuzzy limits of cells separating the four classic nuclear groups and four others taken as being accessory.

History, Ancient↗
PubMed1997

Immunohistochemical detection of schwannomin and neurofibromin in vestibular schwannomas, ependymomas and meningiomas.

In addition to schwannomas, patients with neurofibromatosis type 2 (NF2) frequently develop meningiomas and occasionally, ependymomas. Using DNA and protein analyses, we have shown NF2 gene mutations and lack of the gene product schwannomin in 29 schwannomas, 10 meningiomas, and in 7 ependymomas. We have raised antibodies (ABs) to peptides from the C-terminal (5990-AB) and N-terminal (5991-AB) domains of schwannomin. The ABs specifically detected a 65 kDa protein in a Schwann cell line and recognized schwannomin in the cytoplasm of Schwann cells (SCH), perineurial cells, and vestibular ganglion neurons. None of the 29 schwannomas were stained by the 5990-AB. Only 4 schwannomas were stained by the 5991-AB, indicating that most truncated schwannomins were unstable or not expressed in schwannomas. Seven of 10 meningiomas, including 3 tumors from NF2 patients, were not stained by either 5990-AB or 5991-AB. Only 2 of 7 ependymomas lacked schwannomin. Complete lack of schwannomin in these tumors supports a tumor suppressor function for schwannomin in some meningiomas and ependymomas. All tumors showed staining with an antibody to a C-terminal peptide of neurofibromin, confirming that full-length neurofibromin is present in these vestibular schwannomas, meningiomas, and ependymomas. The presence of schwannomin in some meningiomas and in the majority of ependymomas indicates that additional genes are likely to play a role in tumorigenesis of these tumors.

Brain Neoplasms↗
PubMed1981

Effects of stimulation of frontal cortex, superior colliculus, and neck muscle afferents on interstitiospinal neurons in the cat.

Interstitiospinal neurons were activated by antidromic stimulation of the spinal cord ventromedial funiculus at C1 and C4 in cerebellectomized cats under chloralose anesthesia. Neurons responding only to C1 were classified as N cells and those responding both to C1 and C4 were classified as D cells, as in previous experiments (Fukushima et al. 1980a). Vestibular branching interstitiospinal and reticulospinal neurons were also identified as in the previous experiments. Stimulation of the ipsilateral pericruciate cortex evoked firing in 31% of N cells, 41% of D cells and 35% of the vestibular branching neurons, while stimulation of the contralateral cortex excited 6% of N cells, 29% of D cells and 14% of vestibular branching neurons. Response latencies ranged from 2 to 15 ms after the effective pulse. By measuring the thresholds of activation of these neurons while changing the depth of the stimulating electrodes, and by mapping the cortical areas, it was shown that the lowest threshold areas were in the frontal eye fields and the anterior sigmoid gyrus near the presylvian sulcus (Area 6). Stimulation of the latter area often evoked neck or shoulder muscles contraction. Stimulation in the deep layers of the ipsilateral superior colliculus evoked firing in about 20% of interstitiospinal neurons and about 42% of vestibular branching neurons, with typical latencies 2-3 ms after the effective pulse, while stimulation of the contralateral superior colliculus was rarely effective. N cells and D cells responded similarly. Thresholds for activation were high in the intermediate tectal layers and declined as the electrodes entered the underlying tegmentum. This suggests that the superior colliculus is not the main source of synaptic inputs to these neurons. Low threshold points were found above the deep fiber layer when stimulating electrodes were inserted into the pretectum. Stimulation of the C2 biventer cervicis nerve excited about 8% of N cells, 18% of D cells, and 15% of vestibular branching neurons bilaterally with typical latencies around 10 ms. Similar results were obtained when C2 splenius nerves were stimulated. The fibers responsible for such excitation are probably group II, since stimuli stronger than 1.8 times threshold of the lowest threshold fibers were needed to evoke excitation. Response decrement was often observed when stimuli were repeated at 1/s, while no such decrement was observed at the rate of 1/3 s. When the convergence of cortical and labyrinthine excitatory inputs was studied, 36% of interstitiospinal neurons received single inputs either from the pericruciate cortex or from the labyrinth, 22% of neurons received convergent excitation from both and the remaining 42% did not respond to either stimulus. Although vestibular branching neurons rarely received labyrinthine inputs, they frequently showed convergence of excitation to stimulation of the frontal cortex, superior colliculus and vestibular nuclei.

Afferent Pathways↗
PubMed1987

Immunohistochemical identification of neuron-specific enolase and calbindin in the vestibular receptors of human fetuses.

Immunohistochemical techniques were used to identify neuron-specific enolase (NSE) and calbindin in the vestibular receptors and ganglia of human fetuses at 10 weeks of gestation. NSE was found in vestibular ganglion cells and in a few sensory cells. The pattern of immunoreactivity in the sensory epithelia was characteristic of the appearance of NSE in these structures. Calbindin was found in vestibular ganglion cells and sensory cells which displayed a strong immunoreactivity. These findings are discussed with regard to synaptogenesis and they indicate that the vestibular receptors show biochemical signs of maturation consistent with the possibility of synaptic activity.

Calbindins↗
PubMed1991

[Quantitative study of scarpa ganglion in Menière disease].

The Scarpa ganglia and vestibular nerves were obtained by means of vestibular neurectomy in 4 cases of Menière disease. The nucleoli of nerve cells in Scarpa ganglia were counted in every tenth section under the light microscope (3 cases). The formula of Abercrombie was used to correct the errors introduced by double counting of nucleolus splits between two sections. It was found that counts of ganglion cells in three cases appeared to decline. Although the ultrastructural change of the myelin sheaths was found in another case, it is rather difficult to distinguish this change from that due to surgical trauma.

Adult↗
PubMed1994

Mapping of perineuronal nets in the rat brain stained by colloidal iron hydroxide histochemistry and lectin cytochemistry.

Net-like structures, visualized with the Golgi technique and several histochemical and immunocytochemical methods, have been described to ensheath somata, parts of dendrites and axon initial segments of various types of neurons. The origin and function of these perineuronal nets have been controversially discussed. Recently, it was confirmed that they are glia-associated. In the present study such perineuronal nets were demonstrated by using colloidal iron hydroxide staining for detection of polyanionic components and the plant lectins Vicia villosa agglutinin and Wisteria floribunda agglutinin with affinity for N-acetylgalactosamine. This paper shows their distribution patterns and the occurrence of regional specialization of these nets which might provide a basis to suggest functional implications of these structures. Perineuronal nets were found in more than 100 brain regions, such as neocortex, hippocampus, piriform cortex, basal forebrain complex, dorsal lateral septal nucleus, lateral hypothalamic area, reticular thalamic nucleus, zona incerta, deep parts of superior and inferior colliculus, red nucleus, substantia nigra, some tegmental nuclei, cerebellar nuclei, dorsal raphe and cuneiform nuclei, central gray, trochlear nucleus, pontine and medullar reticular nuclei, superior olivary nucleus and vestibular nuclei. Neurons enwrapped by perineuronal nets not only differ in morphology but also in transmitter content. In neocortical and hippocampal regions there occurs a much higher number of perineuronal nets ensheathing non-pyramidal cells than in paleocortical structures. Most subcortical regions containing perineuronal nets were found to be integrated in motor functions. The findings are discussed with respect to known electrophysiological data of cell types described in our investigation as net-associated. There are some indications that such cells may represent fast firing types.

Animals↗
PubMed1990

[Vestibular compensation. Review of the literature and clinical applications].

Vestibular compensation is an excellent model for the study of plasticity of the adult central nervous system. Therefore it has been the subject of several studies in humans and animals, which will be briefly summed up by the authors. Lesions of the labyrinth or vestibular neurectomy are immediately followed of postural and oculomotor disorders, as well as by dynamic deficits of the various vestibular reflexes (vestibulo-ocular and vestibulonucal reflexes). While the former problems always recede in all species, the restoration of the dynamic properties of vestibular reflexes largely depends upon the species considered, in particular for the vestibulo-ocular reflex. However, this function seems to recover the gain and phase it had prior to the lesion in both humans and monkeys. What is the neuronal substrate of these various deficits? Electrophysiological studies have demonstrated at the acute stage a symmetrical activity between the two vestibular nuclei: on the side of the lesion, the nucleus becomes inactive, while the resting discharge of the contralateral vestibular neurons is increased. Following compensation, symmetric activity is restored between both nuclei due to the regeneration of a new basic discharge in the deafferented neurons. The matter of vestibular compensation can therefore be formulated as follows: which mechanisms enable a central neuron inactivated du to the suppression of most of its excitatory afferences to recover a normal spontaneous activity? Several hypotheses, either pre- or postsynaptic, are currently put forward. Presynaptic hypotheses consider the role of the various afferences of the vestibular nuclei, ie. visual, proprioceptive, commissural, cerebellar and other afferences. In fact, the vestibular nuclei are not merely relays between the labyrinthine receptors and the nuclei of the oculomotor nerves, but actually form real sensorimotor integration centers. Besides the afferences from the vestibular nerve, they receive several other sorts of information, including visual and spinal proprioceptive inputs. An increase in the activity of these afferences, a sprouting of their axon collaterals, may favor the return to a normal basic discharge of the central vestibular neurons. The postsynaptic hypotheses involve either a change in the intrinsic membrane properties of the central vestibular neurons following the lesion, or an increase in the number of receptors located on their surface. More specifically, denervation supersensitivity of the glutamatergic receptors has been put forward as the possible origin of vestibular compensation.

Afferent Pathways↗