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1.
PLoS One ; 18(2): e0273883, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36735686

RESUMEN

BACKGROUND: Galvanic vestibular stimulation (GVS) uses at least one electrode placed on the mastoid process with one or multiple placed over other head areas to stimulate the vestibular system. The exact electrode size used is not given much importance in the literature and has not been reported in several studies. In a previous study, we compared the clinical effects of using different electrode sizes (3 cm2 and 35 cm2) with placebo but with the same injected current, on postural control. We observed significant improvement using the smaller size electrode but not with the bigger size electrode. The goal of this study was to simulate the current flow patterns with the intent to shed light and potentially explain the experimental outcome. METHODS: We used an ultra-high-resolution structural dataset and developed a model to simulate the application of different electrode sizes. We considered current flow in the brain and in the vestibular labyrinth. RESULTS: Our simulation results verified the focality increase using smaller electrodes that we postulated as the main reason for our clinical effect. The use of smaller size electrodes in combination with the montage employed also result in higher induced electric field (E-field) in the brain. CONCLUSIONS: Electrode size and related current density is a critical parameter to characterize any GVS administration as the choice impacts the induced E-field. It is evident that the higher induced E-field likely contributed to the clinical outcome reported in our prior study.


Asunto(s)
Encéfalo , Vestíbulo del Laberinto , Vestíbulo del Laberinto/fisiología , Equilibrio Postural/fisiología , Nervio Vestibular/fisiología , Electrodos , Estimulación Eléctrica/métodos
2.
J Neurosci ; 43(6): 902-917, 2023 02 08.
Artículo en Inglés | MEDLINE | ID: mdl-36604171

RESUMEN

Efferent modulation of vestibular afferent excitability is linked to muscarinic signaling cascades that close low-voltage-gated potassium channels (i.e., KCNQ). Here, we show that muscarinic signaling cascades also depolarize the activation range of hyperpolarization-activated cyclic-nucleotide gated (HCN) channels. We compared the voltage activation range and kinetics of HCN channels and induced firing patterns before and after administering the muscarinic acetylcholine receptor (mAChR) agonist oxotremorine-M (Oxo-M) in dissociated vestibular ganglion neurons (VGNs) from rats of either sex using perforated whole-cell patch-clamp methods. Oxo-M depolarized HCN channels' half-activation voltage (V 1/2) and sped up the rate of activation near resting potential twofold. HCN channels in large-diameter and/or transient firing VGN (putative cell bodies of irregular firing neuron from central epithelial zones) had relatively depolarized V 1/2 in control solution and were less sensitive to mAChR activation than those found in small-diameter VGN with sustained firing patterns (putatively belonging to regular firing afferents). The impact of mAChR on HCN channels is not a direct consequence of closing KCNQ channels since pretreating the cells with Linopirdine, a KCNQ channel blocker, did not prevent HCN channel depolarization by Oxo-M. Efferent signaling promoted ion channel configurations that were favorable to highly regular spiking in some VGN, but not others. This is consistent with previous observations that low-voltage gated potassium currents in VGN are conducted by mAChR agonist-sensitive and -insensitive channels. Connecting efferent signaling to HCN channels is significant because of the channel's impact on spike-timing regularity and nonchemical transmission between Type I hair cells and vestibular afferents.SIGNIFICANCE STATEMENT Vestibular afferents express a diverse complement of ion channels. In vitro studies identified low-voltage activated potassium channels and hyperpolarization-activated cyclic-nucleotide gated (HCN) channels as crucial for shaping the timing and sensitivity of afferent responses. Moreover, a network of acetylcholine-releasing efferent neurons controls afferent excitability by closing a subgroup of low-voltage activated potassium channels on the afferent neuron. This work shows that these efferent signaling cascades also enhance the activation of HCN channels by depolarizing their voltage activation range. The size of this effect varies depending on the endogenous properties of the HCN channel and on cell type (as determined by discharge patterns and cell size). Simultaneously controlling two ion-channel groups gives the vestibular efferent system exquisite control over afferent neuron activity.


Asunto(s)
Canales Regulados por Nucleótidos Cíclicos Activados por Hiperpolarización , Neuronas , Receptores Muscarínicos , Nervio Vestibular , Animales , Ratas , Colinérgicos , Canales Catiónicos Regulados por Nucleótidos Cíclicos/efectos de los fármacos , Canales Catiónicos Regulados por Nucleótidos Cíclicos/metabolismo , Canales Regulados por Nucleótidos Cíclicos Activados por Hiperpolarización/efectos de los fármacos , Canales Regulados por Nucleótidos Cíclicos Activados por Hiperpolarización/metabolismo , Agonistas Muscarínicos/farmacología , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Neuronas/fisiología , Nucleótidos/metabolismo , Canales de Potasio , Receptores Muscarínicos/metabolismo , Oxotremorina/farmacología , Nervio Vestibular/efectos de los fármacos , Nervio Vestibular/metabolismo , Nervio Vestibular/fisiología
3.
Biochem Biophys Res Commun ; 611: 114-117, 2022 06 30.
Artículo en Inglés | MEDLINE | ID: mdl-35487061

RESUMEN

It is well known that the initiation of the reflex arcs of the vertebrate vestibular system occurs in the receptors of the labyrinthine organs which transmit the sensory signals via the ribbon synapses to the vestibular nerve afferents (an interneuron). In invertebrate species, and in particular, the statocyst of pulmonate mollusks, it is thought that the receptors send their axons out of the statocyst in the vestibular connective and establish the first synapse onto cerebral ganglia neurons, thereby bypassing the interneuron in the reflex arc. Morphological and electrophysiological techniques were used in this study to identify the first synapse in the vestibular arc of the mollusk Helix is actually within the vestibular connective on its way from the statocyst to cerebral ganglia. Cerebral interneurons were found that sent their neurites to the vestibular nerve, and thus have the potential to respond to the statocyst output or send efferent input to the statocyst.


Asunto(s)
Interneuronas , Nervio Vestibular , Animales , Fenómenos Electrofisiológicos , Interneuronas/fisiología , Caracoles , Sinapsis/fisiología , Nervio Vestibular/fisiología
4.
Braz J Otorhinolaryngol ; 88 Suppl 1: S91-S96, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-34016567

RESUMEN

INTRODUCTION: Vestibular recruitment is a sign of hyperexcitability of central vestibular neurons and may be characteristic of peripheral vestibular damage. OBJECTIVE: To define the post-caloric recruitment index and its ability to predict the stage of vestibular compensation and peripheral lesion. METHODS: First of all, we demonstrated that larger values in the cold post-caloric stimulation compared to warm stimulation were equivalent to vestibular recruitment observed during the sinusoidal harmonic acceleration test. In the next step, patients with vestibular complaints and asymptomatic controls were submitted to the caloric test. We calculated post-caloric recruitment index for the control group. Among the study group, we analyzed the relation between post-caloric recruitment and unilateral weakness as well as the types of vestibular diagnoses. RESULTS: Mean post-caloric recruitment was 17.06% and 33.37% among the control and study group, respectively. The ratio between post-caloric recruitment and unilateral weakness was 1.3 in the study group. Among recruiting subjects, no significant difference of unilateral weakness from the lesioned or healthy side was observed. We found no differences in vestibular diagnoses between recruiting and non-recruiting subjects. CONCLUSION: Post-caloric recruitment index identified asymmetric vestibular tonus and central compensation. The normal value was established at 17.06%.


Asunto(s)
Neuronas , Nervio Vestibular , Humanos , Nervio Vestibular/fisiología , Neuronas/fisiología
5.
Acta Otolaryngol ; 141(6): 545-550, 2021 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-33827362

RESUMEN

BACKGROUND: Vestibulo-ocular reflex (VOR) function is expected to be normal in patients with presbycusis during sudden head rotations. AIM: This study aimed to determine whether presbycusis was accompanied by vestibular system pathologies. In addition, it was examined whether there was a difference existed between the patients with and without presbycusis in terms of normative data. MATERIALS AND METHODS: A total of 40 individuals were included in the study: 20 in the presbycusis group and 20 in the control group. The vestibular systems of both groups were evaluated using the video head impulse test and videonystagmography. RESULTS: The right and left lateral VOR gain values were decreased in the group with presbycusis compared to the control group. The difference between the two groups in the mean VOR gains in the right lateral canal and left lateral canal were statistically significant (p = .040 and p = .050, respectively). The air caloric tests of all individuals were found to be normal. CONCLUSIONS: This result suggests that the loss of vestibular hair cells and vestibular nerve degeneration in the lateral semicircular canal may be more severe in presbycusis than in the same age group with normal hearing.


Asunto(s)
Células Ciliadas Vestibulares/patología , Presbiacusia/fisiopatología , Reflejo Vestibuloocular , Canales Semicirculares/fisiología , Enfermedades Vestibulares/complicaciones , Nervio Vestibular/fisiología , Anciano , Estudios de Casos y Controles , Femenino , Prueba de Impulso Cefálico , Humanos , Masculino , Persona de Mediana Edad , Nistagmo Patológico/complicaciones , Presbiacusia/complicaciones , Presbiacusia/patología , Pruebas de Función Vestibular , Nervio Vestibular/fisiopatología , Vestíbulo del Laberinto
6.
Sci Rep ; 11(1): 1231, 2021 01 13.
Artículo en Inglés | MEDLINE | ID: mdl-33441862

RESUMEN

Electrical stimulation of the mammalian efferent vestibular system (EVS) predominantly excites primary vestibular afferents along two distinct time scales. Although roles for acetylcholine (ACh) have been demonstrated in other vertebrates, synaptic mechanisms underlying mammalian EVS actions are not well-characterized. To determine if activation of ACh receptors account for efferent-mediated afferent excitation in mammals, we recorded afferent activity from the superior vestibular nerve of anesthetized C57BL/6 mice while stimulating EVS neurons in the brainstem, before and after administration of cholinergic antagonists. Using a normalized coefficient of variation (CV*), we broadly classified vestibular afferents as regularly- (CV* < 0.1) or irregularly-discharging (CV* > 0.1) and characterized their responses to midline or ipsilateral EVS stimulation. Afferent responses to efferent stimulation were predominantly excitatory, grew in amplitude with increasing CV*, and consisted of fast and slow components that could be identified by differences in rise time and post-stimulus duration. Both efferent-mediated excitatory components were larger in irregular afferents with ipsilateral EVS stimulation. Our pharmacological data show, for the first time in mammals, that muscarinic AChR antagonists block efferent-mediated slow excitation whereas the nicotinic AChR antagonist DHßE selectively blocks efferent-mediated fast excitation, while leaving the efferent-mediated slow component intact. These data confirm that mammalian EVS actions are predominantly cholinergic.


Asunto(s)
Colinérgicos/metabolismo , Mamíferos/fisiología , Neuronas Aferentes/fisiología , Neuronas Eferentes/fisiología , Nervio Vestibular/fisiología , Vestíbulo del Laberinto/fisiología , Acetilcolina/metabolismo , Acetilcolina/fisiología , Animales , Axones/metabolismo , Axones/fisiología , Estimulación Eléctrica/métodos , Femenino , Masculino , Mamíferos/metabolismo , Ratones , Ratones Endogámicos C57BL , Neuronas Aferentes/metabolismo , Neuronas Eferentes/metabolismo , Receptores Colinérgicos/metabolismo , Canales Semicirculares/metabolismo , Canales Semicirculares/fisiología , Nervio Vestibular/metabolismo , Vestíbulo del Laberinto/metabolismo
7.
J Neurophysiol ; 124(2): 510-524, 2020 08 01.
Artículo en Inglés | MEDLINE | ID: mdl-32667253

RESUMEN

Vestibular afferent neurons convey information from hair cells in the peripheral vestibular end organs to central nuclei. Primary vestibular afferent neurons can fire action potentials at high rates and afferent firing patterns vary with the position of nerve terminal endings in vestibular neuroepithelia. Terminals contact hair cells as small bouton or large calyx endings. To investigate the role of Na+ currents (INa) in firing mechanisms, we investigated biophysical properties of INa in calyx-bearing afferents. Whole cell patch-clamp recordings were made from calyx terminals in thin slices of gerbil crista at different postnatal ages: immature [postnatal day (P)5-P8, young (P13-P15), and mature (P30-P45)]. A large transient Na+ current (INaT) was completely blocked by 300 nM tetrodotoxin (TTX) in mature calyces. In addition, INaT was accompanied by much smaller persistent Na+ currents (INaP) and distinctive resurgent Na+ currents (INaR), which were also blocked by TTX. ATX-II, a toxin that slows Na+ channel inactivation, enhanced INaP in immature and mature calyces. 4,9-Anhydro-TTX (4,9-ah-TTX), which selectively blocks Nav1.6 channels, abolished the enhanced INa in mature, but not immature, calyces. Therefore, Nav1.6 channels mediate a component of INaT and INaP in mature calyces, but are minimally expressed at early postnatal days. INaR was expressed in less than one-third of calyces at P6-P8, but expression increased with development, and in mature cristae INaR was frequently found in peripheral calyces. INaR served to increase the availability of Na+ channels following brief membrane depolarizations. In current clamp, the rate and regularity of action potential firing decreased in mature peripheral calyces following 4,9-ah-TTX application. Therefore, Nav1.6 channels are upregulated during development, contribute to INaT, INaP, and INaR, and may regulate excitability by enabling higher mean discharge rates in a subpopulation of mature calyx afferents.NEW & NOTEWORTHY Action potential firing patterns differ between groups of afferent neurons innervating vestibular epithelia. We investigated the biophysical properties of Na+ currents in specialized vestibular calyx afferent terminals during postnatal development. Mature calyces express Na+ currents with transient, persistent, and resurgent components. Nav1.6 channels contribute to resurgent Na+ currents and may enhance firing in peripheral calyx afferents. Understanding Na+ channels that contribute to vestibular nerve responses has implications for developing new treatments for vestibular dysfunction.


Asunto(s)
Potenciales de Acción/fisiología , Células Ciliadas Vestibulares/fisiología , Canal de Sodio Activado por Voltaje NAV1.6/fisiología , Bloqueadores de los Canales de Sodio/farmacología , Sodio , Tetrodotoxina/farmacología , Nervio Vestibular/fisiología , Potenciales de Acción/efectos de los fármacos , Factores de Edad , Animales , Gerbillinae , Células Ciliadas Vestibulares/efectos de los fármacos , Canal de Sodio Activado por Voltaje NAV1.6/efectos de los fármacos , Nervio Vestibular/efectos de los fármacos
8.
J Neurophysiol ; 124(2): 360-374, 2020 08 01.
Artículo en Inglés | MEDLINE | ID: mdl-32609559

RESUMEN

In the vestibular peripheral organs, type I and type II hair cells (HCs) transmit incoming signals via glutamatergic quantal transmission onto afferent nerve fibers. Additionally, type I HCs transmit via "non-quantal" transmission to calyx afferent fibers, by accumulation of glutamate and potassium in the synaptic cleft. Vestibular efferent inputs originating in the brainstem contact type II HCs and vestibular afferents. Here, synaptic inputs to type II HCs were characterized by using electrical and optogenetic stimulation of efferent fibers combined with in vitro whole cell patch-clamp recording from type II HCs in the rodent vestibular crista. Properties of efferent synaptic currents in type II HCs were similar to those found in cochlear HCs and mediated by activation of α9-containing nicotinic acetylcholine receptors (nAChRs) and small-conductance calcium-activated potassium (SK) channels. While efferents showed a low probability of release at low frequencies of stimulation, repetitive stimulation resulted in facilitation and increased probability of release. Notably, the membrane potential of type II HCs during optogenetic stimulation of efferents showed a strong hyperpolarization in response to single pulses and was further enhanced by repetitive stimulation. Such efferent-mediated inhibition of type II HCs can provide a mechanism to adjust the contribution of signals from type I and type II HCs to vestibular nerve fibers, with a shift of the response to be more like that of calyx-only afferents with faster non-quantal responses.NEW & NOTEWORTHY Type II vestibular hair cells (HCs) receive inputs from efferent neurons in the brain stem. We used in vitro optogenetic and electrical stimulation of vestibular efferent fibers to study their synaptic inputs to type II HCs. Stimulation of efferents inhibited type II HCs, similar to efferent effects on cochlear HCs. We propose that efferent inputs adjust the contribution of signals from type I and II HCs to vestibular nerve fibers.


Asunto(s)
Tronco Encefálico/fisiología , Células Ciliadas Vestibulares/fisiología , Neuronas Eferentes/fisiología , Receptores Nicotínicos/fisiología , Potenciales Sinápticos/fisiología , Nervio Vestibular/fisiología , Animales , Estimulación Eléctrica , Femenino , Masculino , Ratones , Ratones de la Cepa 129 , Optogenética , Técnicas de Placa-Clamp , Ratas , Ratas Sprague-Dawley
9.
Med Biol Eng Comput ; 58(4): 701-708, 2020 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-31953797

RESUMEN

Electrical stimulus is one of the common stimulating methods, and Galvanic vestibular stimulation (GVS) is the oldest form as an electrical stimulation. Nevertheless, GVS is still considered as a secondary stimulating tool for the medical purposes. Even though some unarguable findings have made using GVS, its use has been limited because of its ambiguity as an input source. For better understanding, many previous studies mainly focused on its functional effects, like the ocular reflexes. However, its fundamental effects on the neural activities are still elusive, such as the dominant influences by different parameters of GVS. Here we compared the effects on the neuronal responses by applying two different parameters, strength and rate, of GVS. To assess the dominance on the neuronal responses to these parameters, we designed three independent stimuli. Those stimuli were multiply applied to obtain the responding slopes based on the mechanism of non-associative learning processes, and the effects on the neurons were calculated as an inner angle between two responding slopes. Out of 23 neurons, 15 (65.2%) units were affected more by the strength with a statistical significance (p = 0.047). The ranges of the inner angles also implied the strength (- 3.354°~2.063°) mainly modulated by the neuronal responses comparing with those by the rate (- 2.001°~1.975°). The dominance of the parameters was closely related with the neuronal sensitivity to stimulation (SE) (p = 0.018), while there were few relations with the neuronal regularity, directional preference (DP), and the physiological response (PR) (p > 0.059). Thus, the neural information related with the dominance was delivered by the irregular neurons, and these types of neurons should be the targets for the stimulation. Graphical abstract.


Asunto(s)
Estimulación Eléctrica/métodos , Vestíbulo del Laberinto/fisiología , Animales , Cobayas , Aprendizaje , Modelos Animales , Neuronas/fisiología , Nervio Vestibular/fisiología , Núcleos Vestibulares/fisiología
10.
Brain Stimul ; 13(1): 60-68, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-31636023

RESUMEN

OBJECTIVE: Vestibular afferents converge with nociceptive ones within the posterior insula, and can therefore modulate nociception. Consistent with this hypothesis, caloric vestibular stimulation (CVS) has been shown to reduce experimental and clinical pain. Since CVS can induce undesirable effects in a proportion of patients, here we explored an alternative means to activate non-invasively the vestibular pathways using innocuous bi-mastoid galvanic stimulation (GVS), and assessed its effects on experimental pain. METHODS: Sixteen healthy volunteers participated in this study. Experimental pain was induced by noxious laser-heat stimuli to the left hand while recording pain ratings and related brain potentials (LEPs). We evaluated changes of these indices during left- or right-anodal GVS (cathode on contralateral mastoid), and contrasted them with those during sham GVS, optokinetic vestibular stimulation (OKS) using virtual reality, and attentional distraction to ascertain the vestibular-specific analgesic effects of GVS. RESULTS: GVS elicited brief sensations of head/trunk deviation, inoffensive to all participants. Both active GVS conditions showed analgesic effects, greater for the right anodal stimulation. OKS was helpful to attain significant LEP reductions during the left-anodal stimulation. Neither sham-GVS nor the distraction task were able to modulate significantly pain ratings or LEPs. CONCLUSIONS: GVS appeared as a well-tolerated and powerful procedure for the relief of experimental pain, probably through physiological interaction within insular nociceptive networks. Either isolated or in combination with other types of vestibular activation (e.g., optokinetic stimuli), GVS deserves being tested in clinical settings.


Asunto(s)
Corteza Cerebral/fisiología , Terapia por Estimulación Eléctrica/métodos , Respuesta Galvánica de la Piel/fisiología , Nocicepción/fisiología , Manejo del Dolor/métodos , Nervio Vestibular/fisiología , Adolescente , Adulto , Femenino , Calor/efectos adversos , Humanos , Masculino , Dolor/diagnóstico , Dolor/fisiopatología , Dimensión del Dolor/métodos , Adulto Joven
11.
J Neurophysiol ; 123(2): 608-629, 2020 02 01.
Artículo en Inglés | MEDLINE | ID: mdl-31800345

RESUMEN

It has been over 60 years since peripheral efferent vestibular terminals were first identified in mammals, and yet the function of the efferent vestibular system remains obscure. One reason for the lack of progress may be due to our deficient understanding of the peripheral efferent synapse. Although vestibular efferent terminals were identified as cholinergic less than a decade after their anatomical characterization, the cellular mechanisms that underlie the properties of these synapses have had to be inferred. In this review we examine how recent mammalian studies have begun to reveal both nicotinic and muscarinic effects at these terminals and therefore provide a context for fast and slow responses observed in classic electrophysiological studies of the mammalian efferent vestibular system, nearly 40 years ago. Although incomplete, these new results together with those of recent behavioral studies are helping to unravel the mysterious and perplexing action of the efferent vestibular system. Armed with this information, we may finally appreciate the behavioral framework in which the efferent vestibular system operates.


Asunto(s)
Acetilcolina/metabolismo , Células Ciliadas Vestibulares/fisiología , Neuronas Eferentes/fisiología , Receptores Colinérgicos/metabolismo , Transmisión Sináptica/fisiología , Nervio Vestibular/fisiología , Animales , Células Ciliadas Vestibulares/metabolismo , Neuronas Eferentes/metabolismo , Nervio Vestibular/metabolismo
12.
Sci Rep ; 9(1): 18924, 2019 12 12.
Artículo en Inglés | MEDLINE | ID: mdl-31831760

RESUMEN

Recent studies have shown that ionic direct current (iDC) can modulate the vestibular system in-vivo, with potential benefits over conventional pulsed stimulation. In this study, the effects of iDC stimulation on vestibular nerve fiber firing rate was investigated using loose-patch nerve fiber recordings in the acutely excised mouse crista ampullaris of the semicircular canals. Cathodic and anodic iDC steps instantaneously reduced and increased afferent spike rate, with the polarity of this effect dependent on the position of the stimulating electrode. A sustained constant anodic or cathodic current resulted in an adaptation to the stimulus and a return to spontaneous spike rate. Post-adaptation spike rate responses to iDC steps were similar to pre-adaptation controls. At high intensities spike rate response sensitivities were modified by the presence of an adaptation step. Benefits previously observed in behavioral responses to iDC steps delivered after sustained current may be due to post-adaptation changes in afferent sensitivity. These results contribute to an understanding of peripheral spike rate relationships for iDC vestibular stimulation and validate an ex-vivo model for future investigation of cellular mechanisms. In conjunction with previous in-vivo studies, these data help to characterize iDC stimulation as a potential therapy to restore vestibular function after bilateral vestibulopathy.


Asunto(s)
Potenciales de Acción/fisiología , Adaptación Fisiológica , Modelos Neurológicos , Nervio Vestibular/fisiología , Vestíbulo del Laberinto/fisiología , Animales , Femenino , Transporte Iónico/fisiología , Masculino , Ratones , Ratones Transgénicos
13.
J Int Adv Otol ; 15(2): 304-308, 2019 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-31418719

RESUMEN

OBJECTIVES: CANVAS is an acronym for cerebellar ataxia, neuropathy and vestibular areflexia syndrome. Limited autopsy data has suggested that CANVAS is caused by a focal dorsal root ganglionopathy that damages Scarpa's (vestibular) ganglion, but spares the Spiral (hearing) ganglion. If the vestibular areflexia of CANVAS is in fact due to ganglionopathy, then there should be global reduction of all vestibular responses. MATERIALS AND METHODS: With this hypothesis in mind, a retrospective review of 5 subjects who met the clinical criteria for CANVAS was performed. Recent advances in vestibular testing have made it possible to quantify responses from all 5 vestibular end organs in the inner ear. Results of the Video head impulse test (VHIT), video oculography, caloric test and vestibular evoked myogenic potential (VEMP) were examined to determine if all 5 end organs are nonfunctional in CANVAS. RESULTS: Severe reduction of function of the six semicircular canals and ocular VEMPs were observed. Only the cervical VEMPs were present and reproducible, consistent with either partial sparing of the inferior vestibular ganglia, specific embryologic resistance of the saccule to the degeneration or a mechanism for cervical VEMPs that does not require an intact vestibular ganglion. CONCLUSION: Our results suggest that Scarpa´s ganglia dysfunction could be the mechanism for loss of semicircular canal and utricular function in CANVAS patients, but the preservation of the cervical VEMP response is unexplained.


Asunto(s)
Vestibulopatía Bilateral/fisiopatología , Ataxia Cerebelosa/fisiopatología , Anciano , Anciano de 80 o más Años , Femenino , Prueba de Impulso Cefálico , Humanos , Masculino , Persona de Mediana Edad , Reflejo Vestibuloocular/fisiología , Estudios Retrospectivos , Canales Semicirculares/fisiología , Síndrome , Potenciales Vestibulares Miogénicos Evocados/fisiología , Nervio Vestibular/fisiología , Vestíbulo del Laberinto/fisiología
14.
J Neurosci ; 39(35): 6922-6935, 2019 08 28.
Artículo en Inglés | MEDLINE | ID: mdl-31285300

RESUMEN

A group of vestibular afferent nerve fibers with irregular-firing resting discharges are thought to play a prominent role in responses to fast head movements and vestibular plasticity. We show that, in C57BL/6 mice (either sex, 4-5 weeks old), normal activity in the efferent vestibular pathway is required for function of these irregular afferents. Thermal inhibition of efferent fibers results in a profound inhibition of irregular afferents' resting discharges, rendering them inadequate for signaling head movements. In this way, efferent inputs adjust the contribution of the peripheral irregular afferent pathway that plays a critical role in peripheral vestibular signaling and plasticity.SIGNIFICANCE STATEMENT Vestibular end organs in the inner ear receive efferent inputs from the brainstem. Previously, electrical stimulation of efferents was linked to an increase in resting discharges of afferents and a decrease in their sensitivities. Here, we show that localized thermal inhibition of unmyelinated efferents results in a significant decrease in the activity of afferent nerve fibers, particularly those with irregular resting discharges implicated in responses to fast head movements and vestibular compensation. Thus, by upregulating and downregulating of afferent firing, particularly irregular afferents, efferents adjust neural activity sensitive to rapid head movements. These findings support the notion that peripheral vestibular end organs are not passive transducers of head movements and their sensory signal transmission is modulated by efferent inputs.


Asunto(s)
Potenciales de Acción/fisiología , Neuronas Aferentes/fisiología , Neuronas Eferentes/fisiología , Nervio Vestibular/fisiología , Vías Aferentes/fisiología , Animales , Femenino , Movimientos de la Cabeza/fisiología , Masculino , Ratones
15.
Nat Commun ; 10(1): 1904, 2019 04 23.
Artículo en Inglés | MEDLINE | ID: mdl-31015434

RESUMEN

Galvanic vestibular stimulation (GVS) uses the external application of electrical current to selectively target the vestibular system in humans. Despite its recent popularity for the assessment/treatment of clinical conditions, exactly how this non-invasive tool activates the vestibular system remains an open question. Here we directly investigate single vestibular afferent responses to GVS applied to the mastoid processes of awake-behaving monkeys. Transmastoid GVS produces robust and parallel activation of both canal and otolith afferents. Notably, afferent activation increases with intrinsic neuronal variability resulting in constant GVS-evoked neuronal detection thresholds across all afferents. Additionally, afferent tuning differs for GVS versus natural self-motion stimulation. Using a stochastic model of repetitive activity in afferents, we largely explain the main features of GVS-evoked vestibular afferent dynamics. Taken together, our results reveal the neural substrate underlying transmastoid GVS-evoked perceptual, ocular and postural responses-information that is essential to advance GVS applicability for biomedical uses in humans.


Asunto(s)
Potenciales de Acción/fisiología , Potenciales Evocados Somatosensoriales/fisiología , Movimientos Oculares/fisiología , Postura/fisiología , Nervio Vestibular/fisiología , Vestíbulo del Laberinto/fisiología , Vías Aferentes/fisiología , Animales , Conducta Animal/fisiología , Electrodos Implantados , Macaca fascicularis , Masculino , Modelos Neurológicos , Técnicas Estereotáxicas , Procesos Estocásticos , Estimulación Transcraneal de Corriente Directa , Vestíbulo del Laberinto/inervación
16.
J Neurophysiol ; 121(6): 2237-2255, 2019 06 01.
Artículo en Inglés | MEDLINE | ID: mdl-30995162

RESUMEN

Galvanic vestibular stimulation (GVS) plays an important role in the quest to understand sensory signal processing in the vestibular system under normal and pathological conditions. It has become a highly relevant tool to probe neuronal computations and to assist in the differentiation and treatment of vestibular syndromes. Following its accidental discovery, GVS became a diagnostic tool that generates eye movements in the absence of head/body motion. With the possibility to record extracellular and intracellular spikes, GVS became an indispensable method to activate or block the discharge in vestibular nerve fibers by cathodal and anodal currents, respectively. Bernie Cohen, in his attempt to decipher vestibular signal processing, has used this method in a number of hallmark studies that have added to our present knowledge, such as the link between selective electrical stimulation of semicircular canal nerves and the generation of directionally corresponding eye movements. His achievements paved the way for other major milestones including the differential recruitment order of vestibular fibers for cathodal and anodal currents, pronounced discharge adaptation of irregularly firing afferents, potential activation of hair cells, and fiber type-specific activation of central circuits. Previous disputes about the structural substrate for GVS are resolved by integrating knowledge of ion channel-related response dynamics of afferents, fiber type-specific innervation patterns, and central convergence and integration of semicircular canal and otolith signals. On the basis of solid knowledge of the methodology, specific waveforms of GVS are currently used in clinical diagnosis and patient treatment, such as vestibular implants and noisy galvanic stimulation.


Asunto(s)
Estimulación Eléctrica/métodos , Movimientos Oculares/fisiología , Prótesis Neurales , Reflejo Vestibuloocular/fisiología , Potenciales Vestibulares Miogénicos Evocados/fisiología , Nervio Vestibular/fisiología , Vestíbulo del Laberinto/fisiología , Animales , Humanos , Xenopus laevis
17.
J Vestib Res ; 29(2-3): 89-96, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-30856136

RESUMEN

BACKGROUND: Vestibular prostheses emulate normal vestibular function by electrically stimulating the semicircular canals using pulse frequency modulation (PFM). Spontaneous activity at the vestibular nerve may limit the dynamic range elicited by PFM. One proposed solution is the co-application of ionic direct current (iDC) to inhibit this spontaneous activity. OBJECTIVE: We aimed to test the hypothesis that a tonic iDC baseline delivered in conjunction with PFM to the vestibular semicircular canals could improve the dynamic range of evoked eye responses. METHODS: Gentamicin-treated chinchillas were implanted with microcatheter electrodes in the vestibular semicircular canals through which pulsatile and iDC current was delivered. PFM was used to modulate vestibulo-ocular reflex (VOR) once it was adapted to a preset iDC and pulse-frequency baseline. Responses to stimulation were assessed by recording the evoked VOR eye direction and velocity. RESULTS: PFM produced VOR responses aligned to the stimulated canal. Introduction of an iDC baseline lead to a small but statistically significant increase in eye response velocity, without influencing the direction of eye rotation. CONCLUSIONS: Tonic iDC baselines increase the dynamic range of encoding head velocity evoked by pulsatile stimulation, potentially via the inhibition of spontaneous activity in the vestibular nerve.


Asunto(s)
Potenciales de Acción/fisiología , Activación del Canal Iónico/fisiología , Reflejo Vestibuloocular/fisiología , Canales Semicirculares/fisiología , Potenciales Vestibulares Miogénicos Evocados/fisiología , Animales , Chinchilla , Estimulación Eléctrica/instrumentación , Movimientos Oculares , Movimientos de la Cabeza/fisiología , Procedimientos Quirúrgicos Otológicos/instrumentación , Prótesis e Implantes , Rotación , Pruebas de Función Vestibular , Nervio Vestibular/fisiología , Vestíbulo del Laberinto/fisiología
18.
J Exp Psychol Hum Percept Perform ; 45(2): 209-223, 2019 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-30589357

RESUMEN

Vestibular signals allow us to maintain balance and orient ourselves in space. However, the possible contribution of the vestibular sense to the perception of the body as one's own (body ownership) remains poorly understood. The aim of the present study was to investigate how vestibular information contributes to the experience of body ownership using multisensory integration. We conducted 3 studies using a "full-body ownership illusion" induced by virtual reality technology and galvanic vestibular stimulation (GVS); the latter is a technique that allows for the selective stimulation of vestibular afferents. Participants wearing head-mounted displays saw a mannequin's body that was performing a slow swinging movement from a first-person perspective. At the same time, participants were exposed to GVS that elicited vestibular sensations of swinging whole-body movements in the corresponding direction. Perceived ownership of the seen body was measured using questionnaire ratings and skin-conductance responses to a knife threat toward the mannequin. We demonstrated that when participants were exposed to congruent visuo-vestibular information, they perceived a stronger ownership of the mannequin's body compared with when they were exposed to unimodal visual and vestibular conditions or an incongruent visuo-vestibular condition. The findings show that visuo-vestibular congruency is sufficient to increase the feeling of illusory body ownership of a mannequin's body. (PsycINFO Database Record (c) 2019 APA, all rights reserved).


Asunto(s)
Ilusiones/fisiología , Percepción de Movimiento/fisiología , Equilibrio Postural/fisiología , Propiocepción/fisiología , Vestíbulo del Laberinto/fisiología , Adulto , Vías Aferentes/fisiología , Estimulación Eléctrica , Femenino , Respuesta Galvánica de la Piel , Humanos , Masculino , Nervio Vestibular/fisiología , Realidad Virtual , Adulto Joven
19.
PLoS One ; 13(10): e0205869, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-30372453

RESUMEN

For over a century, it has been speculated that the vestibular system transmits information about self-motion to the striatum. There have been inconsistent reports of such a connection, and interest in the subject has been increased by the experimental use of galvanic vestibular stimulation in the treatment of Parkinson's Disease patients. Nonetheless, there are few data available on the effects of vestibular stimulation on neurochemical changes in the striatum. We used in vivo microdialysis to analyse changes in the extracellular levels of amino acids and monoamines in the rat striatum, following electrical vestibular stimulation. Stimulation caused a significant decrease in serine and threonine, compared to the no-stimulation controls (P ≤ 0.005 and P ≤ 0.01, respectively). The ratio of DOPAC:dopamine, decreased on the ipsilateral side following stimulation (P ≤ 0.005). There was a significant treatment x side x intensity interaction for taurine levels (P ≤ 0.002), due to a decrease on the contralateral side in stimulated animals, which varied as a function of current. These results show that peripheral vestibular stimulation causes some neurochemical changes in the striatum and support the view that activaton of the vestibular system exerts effects on the function of the striatum.


Asunto(s)
Cuerpo Estriado/fisiología , Terapia por Estimulación Eléctrica , Enfermedad de Parkinson/terapia , Sistema Nervioso Periférico/fisiología , Ácido 3,4-Dihidroxifenilacético/análisis , Animales , Cuerpo Estriado/metabolismo , Dopamina/análisis , Estimulación Eléctrica , Electrodos , Masculino , Neostriado/metabolismo , Sistema Nervioso Periférico/metabolismo , Ratas , Ratas Wistar , Serina/metabolismo , Taurina/metabolismo , Treonina/metabolismo , Nervio Vestibular/fisiología
20.
Sci Rep ; 8(1): 13819, 2018 09 14.
Artículo en Inglés | MEDLINE | ID: mdl-30218045

RESUMEN

Vertebrate inner ear neurons project into the correct brainstem nuclei region before target neurons become postmitotic, or even in their absence. Moreover, afferents from transplanted ears in frogs have been shown to navigate to vestibular nuclei, suggesting that ear afferents use molecular cues to find their target. We performed heterochronic, xenoplastic, and heterotopic transplantations in chickens to investigate whether inner ear afferents are guided by conserved guidance molecules. We show that inner ear afferents can navigate to the vestibular nuclei following a delay in afferent entry and when the ear was from a different species, the mouse. These data suggest that guidance molecules are expressed for some time and are conserved across amniotes. In addition, we show that chicken ears transplanted adjacent to the spinal cord project dorsally like in the hindbrain. These results suggest that inner ear afferents navigate to the correct dorsoventral brainstem column using conserved cues.


Asunto(s)
Vías Aferentes/fisiología , Oído Interno/inervación , Neuronas Aferentes/fisiología , Animales , Tronco Encefálico/fisiología , Embrión de Pollo , Pollos , Señales (Psicología) , Oído Interno/trasplante , Células Ciliadas Auditivas/fisiología , Ratones , Neuronas , Rombencéfalo/fisiología , Médula Espinal/fisiología , Nervio Vestibular/fisiología
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