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PubMed1985

Choline acetyltransferase activity of the principal vestibular nuclei of rat, studied by micropunch technique.

We have assayed choline acetyltransferase (CAT) activity, as a specific marker for cholinergic neurons, in the vestibular nuclear complex (VNC) as a whole, and in the 4 individual principal vestibular nuclei, dissected by a micropunch technique. The VNC contains a significant amount of CAT activity, comparable to that of hippocampus and frontal cortex. CAT activity is relatively concentrated in the medial vestibular nucleus (MVN), which agrees with studies by others showing a greater concentration of muscarinic receptors in MVN. We conclude that cholinergic systems may play a role in central vestibular function, particularly within the MVN.

Animals↗
PubMed1996

Properties of utricular nerve-activated vestibulospinal neurons in cats.

The axonal pathway, conduction velocities, and locations of the cell bodies of utricular nerve-activated vestibulospinal neurons were studied in decerebrated or anesthetized cats using the collision test of orthodromic and antidromic spikes. For orthodromic stimulation, bipolar tungsten electrodes were placed on the utricular nerve and the other vestibular nerve branches were transected. Monopolar tungsten electrodes were positioned on both sides of the upper cervical segments (C2-4), caudal end of the cervical enlargement (C7-T1), and from the lower thoracic to the upper lumbar segments (T12-L3) and were used for antidromic stimulation of the spinal cord. Another monopolar electrode was also placed in the oculomotor nucleus to study whether utricular nerve-activated vestibulospinal neurons have ascending branches to the oculomotor nucleus. Of the 173 vestibular neurons orthodromically activated by the stimulation of the utricular nerve, 46 were second-order vestibulospinal neurons and 5 were third-order neurons. The majority of the utricular nerve-activated vestibulospinal neurons were located in the rostral part of the descending vestibular nucleus and the caudal part of the ventral lateral nucleus. Seventy-three percent of the utricular nerve-activated vestibulospinal neurons descended through the ipsilateral lateral vestibulospinal tract. Approximately 80% of these neurons reached the cervico-thoracic junction, but a few reached the upper lumbar spinal cord. Twenty-seven percent of the utricular nerve-activated vestibulospinal neurons descended through the medial vestibulospinal tract or the contralateral vestibulospinal tracts. Those axons terminated mainly in the upper cervical segments. Almost none of the utricular nerve-activated vestibular neurons had ascending branches to the oculomotor nucleus.

Afferent Pathways↗
PubMed2004

Otx2, Gbx2, and Fgf8 expression patterns in the chick developing inner ear and their possible roles in otic specification and early innervation.

The chick inner ear is a complex structure containing auditory and vestibular sensory organs innervated by neurons of the acoustic-vestibular ganglion. The molecular signals involved in the specification and initial innervation of the otic epithelium are poorly understood. Here, we present a detailed description of the Otx2, Gbx2, and Fgf8 gene expression patterns in the chick developing inner ear, comparing them with the Bmp4 expression, a putative sensory-organ marker. The Otx2 expression was detected in the ventro-lateral wall of the otic anlage and could play a role in the segregation of the saccule and utricle maculae. The relationship between Gbx2 and Fgf8 expression changed during inner ear development but was always related to the macula sacculi innervation and endolymphatic duct formation. Our results also suggest that the maculae of the saccule and lagena, and the medial portion of the macula utriculi could arise within a broad Fgf8-positive domain previously observed at the otocyst stage. The spatial and temporal relationships between these gene expression domains and the initial innervation of the epithelium by some subpopulations of otic axons suggest that expression domain boundaries could be involved in the specification and early innervation of presumptive sensory patches.

Animals↗
PubMed1984

Purkinje cell activity in the primate flocculus during optokinetic stimulation, smooth pursuit eye movements and VOR-suppression.

Purkinje cell (PC) activity in the flocculus of trained monkeys was recorded during: 1) Vestibular stimulation in darkness. 2) Suppression of the vestibulo-ocular reflex (VOR-supp) by fixation of a small light spot stationary with respect to the monkey. 3) Visual-vestibular conflict (i.e. the visual surround moves together with the monkey during vestibular stimulation), which leads to attenuation or suppression of vestibular nystagmus. 4) Smooth pursuit eye movements. 5) Optokinetic nystagmus (OKN). 6) Suppression of nystagmus during optokinetic stimulation (OKN-supp) by fixation of a small light spot; whereby stimulus velocity corresponds then to image slip velocity. Results were obtained from PCs, which were activated with VOR-supp during rotation to the ipsilateral side. The same PCs were also modulated during smooth pursuit and visual-vestibular conflict. No tonic modulation during constant velocity OKN occurred with slow-phase nystagmus velocities below 40-60 deg/s. Tonic responses were only seen at higher nystagmus velocities. Transient activity changes appeared at the beginning and end of optokinetic stimulation. PCs were not modulated by image slip velocity during OKN-supp. The results show that in primates the same population of floccular PCs is involved in different mechanisms of visual-vestibular interaction and that smooth pursuit and certain components of OKN slow-phase velocity share the same neural pathway. It is argued that the activity of these neurons can neither be related strictly to gaze, eye or image slip velocity; instead, their activity pattern can be best interpreted by assuming a modulation, which is complementary to that of central vestibular neurons of the vestibular nuclei, in the control of slow eye movements.

Animals↗
PubMedDate not supplied

Central and peripheral components of short latency vestibular responses in the chicken.

Far-field recordings of short latency vestibular responses to pulsed cranial translation are composed of a series of positive and negative peaks occurring within 10 ms following stimulus onset. In the bird, these vestibular evoked potentials (VsEPs) can be recorded noninvasively and have been shown in the chicken and quail to depend strictly upon the activation of the vestibular component of the eighth nerve. The utility of the VsEP in the study of vestibular systems is dependent upon a clear understanding of the neural sources of response components. The primary aim of the current research in the chicken was to critically test the hypotheses that 1) responses are generated by both peripheral and central neurons and 2) peaks P1 and N1 originate from first order vestibular neurons, whereas later waves primarily depend on activity in higher order neurons. The principal strategy used here was to surgically isolate the eighth nerve as it enters the brainstem. Interruption of primary afferents of the eighth nerve in the brainstem substantially reduced or eliminated peaks beyond P2, whereas P1 and N1 were generally spared. Surgical sections that spared vestibular pathways had little effect on responses. The degree of change in response components beyond N1 was correlated with the extent of damage to central vestibular relays. These findings support the conclusion that responses are produced by both peripheral and central elements of the vestibular system. Further, response peaks later than N1 appear to be dependent upon central relays, whereas P1 and N1 reflect activity of the peripheral nerve. These findings clarify the roles of peripheral and central neurons in the generation of vestibular evoked potentials and provide the basis for a more useful and detailed interpretation of data from vestibular response testing.

Animals↗
PubMed1992

Responses of neurons in the caudal medullary raphe nuclei of the cat to stimulation of the vestibular nerve.

In the decerebrate cat, recordings were made from neurons in the caudal medullary raphe nuclei to determine if they responded to electrical stimulation of the vestibular nerve and thus might participate in vestibulosympathetic reflexes. Many of these cells projected to the upper thoracic spinal cord. The majority (20/28) of raphespinal neurons with conduction velocities between 1 and 4 m/s received vestibular inputs; 13 of the 20 were inhibited, and 7 were excited. Since many raphespinal neurons with similar slow conduction velocities are involved in the control of sympathetic outflow, as well as in other functions, these cells could potentially relay vestibular signals to sympathetic preganglionic neurons. The onset latency of the vestibular effects was long (median of 15 ms), indicating the inputs were polysynaptic. In addition, 34 of 42 raphespinal neurons with more rapid conduction velocities (6-78 m/s) also received long-latency (median of 10 ms) labyrinthine inputs; 26 were excited and 8 were inhibited. Although little is known about these rapidly-conducting cells, they do not appear to be involved in autonomic control, suggesting that the function of vestibular inputs to raphe neurons is not limited to production of vestibulosympathetic reflexes. One hypothesis is that raphe neurons are also involved in modulating the gain of vestibulocollic and vestibulospinal reflexes; this possibility remains to be tested.

Animals↗
PubMed1998

Evidence for three additional P2X2 purinoceptor isoforms produced by alternative splicing in the adult rat vestibular end-organs.

P2X2 receptors are ligand-gated ion channels that are activated by extracellular ATP. To characterize the expression of P2X2 purinoceptor in the adult rat vestibular periphery, reverse transcription-polymerase chain reaction (RT-PCR) was used. No transcript for P2X2 receptor was found in the vestibular primary afferent neurons (Scarpa's ganglia); however, partial cDNAs encoding four splice variants of the P2X2 receptor were isolated from vestibular end-organs. In all four cDNAs, the deletions were of different lengths but started at the same position on the P2X2 gene (Val-370 codon) located toward the intracellular carboxyl terminus. One of these receptor isoforms was identical in sequence to the recently published P2X2(b) receptor (Simon et al., 1997, Mol. Pharmacol. 52, 237-248) (also known as P2X2-2, in the nomenclature of Brändle et al., 1997, FEBS Lett. 404, 294-298). The remaining three novel splice variants of the P2X2 receptor were designated P2X2(e), P2X2(f) and P2X2(g) (GenBank accession numbers AF028603, AF028604 and AF028605, respectively). The functional significance of these three splice variants remains to be determined. Pituitary and cerebellum were used as survey tissues and only the P2X2(b) receptor cDNA was found.

Alternative Splicing↗
PubMed1998

Chicken (Gallus domesticus) inner ear afferents.

Neurons from the vestibular (VG) and the statoacoustic (SAG) ganglion of the chick (Gallus domesticus) were evaluated histologically and morphometrically. Embryos at stages 34 (E8 days), 39 (E13 days) and 44 (E18 days) were sacrificed and temporal bones microdissected. Specimens were embedded in JB-4 methacrylate plastic, and stained with a mixture of 0.2% toluidine blue (TB) and 0.1% basic Fuschin in 25% ethanol or with a mixture of 2% TB and 1% paraphenylenediamine (PDA) for axon and myelin measurement study. Images of the VIIIth nerve were produced by a V150 (R) color imaging system and the contour of 200-300 neuronal bodies (perikarya) was traced directly on a video screen with a mouse in real time. The cross-sectional area of VG perikarya was 67.29 micrometers2 at stage 34 (E8), 128.46 micrometers2 at stage 39 (E13) and 275.85 micrometers2 at stage 44 (E18). The cross-sectional area of SAG perikarya was 62.44 micrometers2 at stage 34 (E8), 102.05 micrometers2 at stage 39 (E13) and 165.02 micrometers2 at stage 44 (E18). A significant cross-sectional area increase of the VG perikarya between stage 39 (E13) and stage 44 (E18) was determined. We randomly measured the cross-sectional area of myelin and axoplasm of hatchling afferent nerves, and found a correspondence between axoplasmic and myelin cross-sectional area in the utricular, saccular and semicircular canal nerve branches of the nerve. The results suggest that the period between stage 34 (E8) and 39 (E13) is a critical period for afferent neuronal development. Physiological and behavioral vestibular properties of developing and maturing hatchlings may change accordingly. The results compliment previous work by other investigators and provide valuable anatomical measures useful to correlate physiological data obtained from stimulation of the whole nerve or its parts.

Animals↗
PubMed1997

Corticovestibular interactions: anatomy, electrophysiology, and functional considerations.

This review summarizes anatomical and electrophysiological observations related to corticovestibular interactions as a step toward understanding their possible functions. Vestibular information is represented in at least three distinct regions of the cerebral cortex in cats and monkeys: the parietal and somatosensory cortex and the parietoinsular vestibular cortex. In addition, vestibular-related signals are found in more extensive regions, including the motor and premotor regions and frontal eye fields. Most of these regions also project directly to the vestibular nuclei. In monkeys, at least six cortical regions have been identified, including the motor, somatosensory, parietal and temporal areas. Most of these regions receive vestibular projections via the thalamus. Most neurons in those cortical areas respond to head velocity and receive converging vestibular, visual and somatosensory input. Electrical stimulation of some of these cortical areas in anesthetized cats influences the activity of many vestibular nuclear neurons including those projecting to the spinal cord. Lesions of the parietal vestibular regions impair the vestibulo-ocular reflex (VOR) and visual suppression of the VOR as well as vestibular-related cognitive functions such as spatial perception and memory in human subjects. Diffuse cortical damage also results in similar impairment of the VOR and suppression of the VOR and possibly the vestibulo-collic reflex. Such impairments after cortical lesions may well be due in part to interruption of cortico-vestibular connections. Future studies in alert animals should focus on the role of different cortical regions projecting to the vestibular nuclei, specifically on how each affects the processing of vestibular signals that mediate vestibulo-motor reflexes and that are used for vestibular related cognitive processes.

Animals↗
PubMed2004

Dynamics and the single spike.

Responses of vestibular primary afferent neurons to head rotation exhibit fractional-order dynamics. As a consequence, the head tends to be in a localized region of its state-space at spike times of a particular neuron during arbitrary head movements, and single spikes can be interpreted as state measurements. We are developing a model of neural computations underlying trajectory prediction and control tasks, based on this experimental observation. This is a step toward a formal neural calculus in which single spikes are modeled realistically as the operands of neural computation.

Action Potentials↗
PubMed1991

The electrically evoked vestibulo-ocular reflex: I. Normal subjects.

Recent animal studies indicate that electric currents applied through perilymphatic-space electrodes stimulate vestibular primary afferent neurons directly. These findings suggest that electrical stimulation may provide a testing method by which the vestibular nerve and central pathways could be evaluated separately from the vestibular end-organ. The goal of this study was to obtain normative data on human beings for an electrically evoked vestibulo-ocular reflex (EVOR). Sinusoidal electrical stimuli (0.0125 to 0.8 Hz, 4 mA peak intensity) were applied along the interaural axis through mastoid electrodes in 10 subjects. Horizontal eye movements were recorded by an infrared limbus-tracking device. The subjects also underwent rotational stimulation at the same frequencies so that their horizontal vestibulo-ocular reflex (VOR) could be evaluated. Nystagmus was observed in the EVOR at lower stimulus frequencies, whereas purely sinusoidal eye deviations occurred at higher frequencies. The phase of the EVOR slow-component eye velocity consistently lagged the stimulus. This contrasts with the phase measurements of the VOR in the same subjects, which exhibited a lead relative to head velocity. These findings suggest that currents applied to human beings may activate vestibular primary afferents independent of peripheral receptor mechanisms and thereby provide a "site-of-lesion" testing method by which the vestibular nerve and central pathways can be evaluated separately from the vestibular end-organ.

Adolescent↗
PubMed1993

Responses of neurons in the rostral ventrolateral medulla of the cat to natural vestibular stimulation.

To investigate the neural substrate of vestibulo-sympathetic reflexes, we studied the responses of neurons in the rostral ventrolateral medulla (RVLM) of decerebrate cats to natural stimulation of the labyrinth in vertical and horizontal planes. The RVLM is a major source of excitatory inputs to sympathetic preganglionic neurons. The animals used in these studies were baroreceptor-denervated and vagotomized and had a cervical spinal transection so that inputs from tilt-sensitive receptors outside of the labyrinth did not influence the units we recorded. Of the 38 neurons whose type of vertical vestibular inputs could be classified, the majority (27) received signals mainly from otolith organs. Only 4 of the neurons received inputs predominantly from vertical semicircular canals, and 7 were classified as having convergent inputs from otoliths and canals that were spatially aligned (2 cells) or misaligned (5 cells). In addition, only 2 of 68 neurons tested responded to sinusoidal horizontal rotations in a manner typical of brainstem neurons that receive inputs from the horizontal semicircular canals. Thus, the vestibular inputs to the RVLM appear to come mainly from otolith receptors. In labyrinthectomized cats, we were unable to locate neurons with responses to tilt similar to those of cells recorded in labyrinth-intact cats, confirming that the responses attributed to vertical vestibular inputs were produced by signals from the labyrinth. In animals whose semicircular canals had been rendered dysfunctional by plugging, we only recorded responses similar to those of neurons classified as having mainly otolith inputs in canal-intact animals, indicating that the dynamic behavior of these cells does not depend upon canal inputs. The presence of otolith inputs to the RVLM is consistent with the hypothesis that this region mediates vestibulo-sympathetic reflexes involved in correcting posturally-related changes in blood pressure.

Animals↗
PubMed1995

Neuronal deficits, not involving motor neurons, in mice lacking BDNF and/or NT4.

Nerve growth factor and other neurotrophins signal to neurons through the Trk family of receptor tyrosine kinases. TrkB is relatively promiscuous in vitro, acting as a receptor for brain-derived neurotrophic factor (BDNF), neurotrophin-4 (NT4) and, to a lesser extent, NT3 (refs 3-5). Mice lacking TrkB show a more severe phenotype than mice lacking BDNF, suggesting that TrkB may act as a receptor for additional ligands in vivo. To explore this possibility, we generated mice lacking NT4 or BDNF as well as mice lacking both neurotrophins. Unlike mice lacking other Trks or neurotrophins, NT4-deficient mice are long-lived and show no obvious neurological defects. Analysis of mutant phenotypes revealed distinct neuronal populations with different neurotrophin requirements. Thus vestibular and trigeminal sensory neurons require BDNF but not NT4, whereas nodose-petrosal sensory neurons require both BDNF and NT4. Motor neurons, whose numbers are drastically reduced in mice lacking TrkB, are not affected even in mice lacking both BDNF and NT4. These results suggest that another ligand, perhaps NT3, does indeed act on TrkB in vivo.

Animals↗
PubMed2002

Role of the vestibular nuclei in endothelin-1-induced barrel rotation in rats.

The fourth or lateral ventricular injection of endothelin-1 resulted in a dose-dependent increase in the barrel rotation and produced marked induction of c-Fos-positive cells in the vestibular nuclei. The doses of the former injection were lower and had shorter mean latent periods compared with the later injection. c-Fos expression after endothelin-1 injection was prevented by the pretreatment with the endothelin ET(A) receptor antagonist, cyclo(D-alpha-aspartyl-L-propyl-D-valyl-L-leucyl-D-tryptophyl) (BQ-123), the glutamate NMDA receptor antagonist, dizocilpine maleate (MK-801), or the L-type Ca(2+) channel antagonist, verapamil, in addition to the incidence of the rotational behavior. There was a significant difference in c-Fos expression between the right and left medial vestibular nuclei, and the number of c-Fos-labeled neurons in the medial vestibular nucleus was markedly increased on the opposite side of the rotational direction. These results suggest that the elicitation of the barrel rotation may be mediated by endothelin ET(A) receptors, glutamate NMDA receptors, and L-type Ca(2+) channels. The changes in the receptor and channel systems induced by endothelin-1 injections appeared to exert crucial influences on the vestibular nuclei and then on the maintenance of equilibrium. The direction of the barrel rotation has a deep connection with the imbalance of neuronal activity in the left and right medial vestibular nuclei.

Animals↗
PubMed2004

Immunohistochemical detection of phosphorylated form of extracellular signal-regulated kinase 1/2 in rat vestibular nuclei following hemorrhagic hypotension.

The purpose of this study was to evaluate the expression of the phosphorylated form of extracellular-regulated protein kinase 1/2 (pERK1/2), which is one of the major regulatory factors for transcription of the c-fos oncogene in neurons, within the vestibular nuclei (VN) of rats following acute arterial hypotension. Following acute arterial hypotension induced by rapid hemorrhage, a significant number of pERK1/2-immunoreactive neurons appeared bilaterally in the caudal aspect of the medial and inferior VN. No labeling of pERK1/2 was observed in the lateral VN. The peak expression of pERK1/2-immunoreactive neurons in these nuclei occurred within 5 min after hemorrhage. In bilaterally labyrinthectomized rats, the appearance of pERK1/2-immunoreactive neurons was eliminated in the VN. These results suggest that, following acute hypotension, afferent signals from the peripheral vestibular receptors are required for activation of extracellular signal-regulated kinase 1/2 in the VN.

Animals↗
PubMed1987

The early development of neurons with GABA immunoreactivity in the CNS of Xenopus laevis embryos.

We have used an antibody to glutaraldehyde fixation complexes of gamma-amino butyric acid (GABA) to stain the developing central nervous system of Xenopus laevis embryos. Neuronal somata, growth cones, axons, and dendrites were found with GABA-like immunoreactivity. Transmission electron microscope (TEM) observations were made of axons and synapses. By observation of the earliest stages of differentiation of neurons, seven classes of putative GABAergic interneurons were discerned. 1) Ascending neurons are first stained in the hindbrain at stage 26 and later extend caudally in the spinal cord. They have ascending ipsilateral axons. 2) Midhindbrain reticulospinal neurons are first stained at stage 25 and develop as a compact group with descending ipsilateral and contralateral axons. 3) Vestibular complex commissural neurons are first stained at stage 29/30 in a dorsal position near the entry of the seventh and eighth cranial nerves. They have ventral commissural axons that descend contralaterally and their somata form a compact mass. 4) Rostral hindbrain commissural neurons are first stained at stage 33/34 just rostral to the entry of the trigeminal nerve. They each have a decussating projection. 5) Rostral midbrain neurons are first stained in the midbrain at stage 29/30 and are later associated with prominent dorsal and ventral commissures. 6) Optic tract and 7) rostral forebrain neurons are found in the forebrain associated with strongly stained axon tracts. The direction of axonal growth from its earliest stages was distinct for each class of hindbrain and spinal cord neuron.

Animals↗
PubMed1988

Distribution of glycine receptors on the membrane of a central neuron: an immunoelectron microscopy study.

The distribution of glycine receptors on the plasmalemma of the teleost Mauthner cell was examined with light and electron microscopy using monoclonal antibodies raised against the glycine receptors of the rat. These immunoglobulins recognize a peptide of 93 kDa associated with the intracellular side of the receptor complex. With indirect immunofluorescence, labeling appeared as small clusters over the whole surface of the neuron. This distribution indicates that, unlike other neurons, the Mauthner cell can express glycine receptors at the dendritic and at the somatic level as well. Vestibular or reticular neurons lying in the proximity of the Mauthner cell were also stained. At the ultrastructural level, the immunoenzymatic reaction product, localized in front of the presynaptic active zones, slightly overextends the limits of the synaptic complex. This observation may account for vesicular exocytosis at the border of the presynaptic grid. More generally, inside and outside the axon-cap, stained postsynaptic membranes were apposed to terminals identified as unmyelinated club endings and some small vesicle boutons, respectively. Each of them could establish classical flat synapses or spinelike contacts, the latter being described here for the first time. Patches of membrane remained unstained, however, particularly along the lateral and ventral dendrites of the cell; they corresponded to the contact sites of excitatory afferents. In order to enhance the penetration of immunoreactive substances, a particular fixation procedure was used; its effect on the shape of the synaptic vesicles is described. Our results support the notion that glycine is responsible for both somatic and remote dendritic Cl- -dependent inhibition of the Mauthner cell. The first one is produced by the so-called PHP exhibiting neurons, which correspond to cells of recurrent collateral network and vestibulovestibular pathway. In contrast, cells giving rise to the more distal inhibitory synapses on both dendrites are not yet characterized.

Animals↗