Medial Vestibular Nucleus Neurons Research Articles

Neonatal GABAergic transmission primes vestibular gating of output for adult spatial navigation

GABAergic interneurons are poised with the capacity to shape circuit output via inhibitory gating. How early in the development of medial vestibular nucleus (MVN) are GABAergic neurons recruited for feedforward shaping of outputs to higher centers for spatial navigation? The role of early GABAergic transmission in assembling vestibular circuits for spatial navigation was explored by neonatal perturbation. Immunohistochemistry and confocal imaging were utilized to reveal the expression of parvalbumin (PV)-expressing MVN neurons and their perineuronal nets. Whole-cell patch-clamp recording, coupled with optogenetics, was conducted in vitro to examine the synaptic function of MVN circuitry. Chemogenetic targeting strategy was also employed in vivo to manipulate neuronal activity during navigational tests. We found in rats a neonatal critical period before postnatal day (P) 8 in which competitive antagonization of GABAergic transmission in the MVN retarded maturation of inhibitory neurotransmission, as evidenced by deranged developmental trajectory for excitation/inhibition ratio and an extended period of critical period-like plasticity in GABAergic transmission. Despite increased number of PV-expressing GABAergic interneurons in the MVN, optogenetic-coupled patch-clamp recording indicated null-recruitment of these neurons in tuning outputs along the ascending vestibular pathway. Such perturbation not only offset output dynamics of ascending MVN output neurons, but was further accompanied by impaired vestibular-dependent navigation in adulthood. The same perturbations were however non-consequential when applied after P8. Results highlight neonatal GABAergic transmission as key to establishing feedforward output dynamics to higher brain centers for spatial cognition and navigation.

A Case of Neural Integrator Failure in Vitamin B1 Deficiency. (P1-9.004)

<h3>Objective:</h3> Case Report <h3>Background:</h3> The nucleus prepositus hypoglossi (NPH) and medial vestibular nuclei (MVN) are two closely related neural integrators situated in the brainstem responsible for horizontal conjugate eye movement. Thiamine deficiency, a hallmark of Wernicke’s encephalopathy, affects the MVN to a greater extent. We report a case of impaired horizontal gaze holding post-sleeve gastrectomy secondary to Vitamin B1 deficiency. <h3>Design/Methods:</h3> A 24-year-old female presented with new onset diplopia on lateral gaze, dizziness, and lower limb distal paraesthesia eight weeks post-sleeve gastrectomy. Examination revealed conjugate eye movements and horizontal gaze-holding failure bilaterally, with intact convergence and vertical gaze. Normal discs were observed on fundoscopy with no retinal haemorrhages, and visual acuity preserved. She had a normal mental state with mild sensory ataxia. Reflexes were present and symmetrical. <h3>Results:</h3> Cerebrospinal fluid analysis was normal, and MRI Brain showed no acute infarction, haemorrhage, or brainstem lesions. Folate, Vitamin B6, B12, and HbA1c levels were within normal range, with a negative infective screen. Vitamin B1 level was found to be low at 44.3nmol/L (normal range: 66.5–200nmol/L). She was commenced on high-dose intravenous thiamine for one week with symptomatic improvement in diplopia and subsequently discharged on long-term thiamine supplementation. <h3>Conclusions:</h3> The high metabolic requirements of MVN neurons responsible for high acceleration horizontal vestibulo-ocular reflex (VOR) is postulated to account for the selective vulnerability to thiamine deprivation. This case highlights an unusual presentation of disruption in horizontal gaze-holding mechanisms through failure of neural integrators, particularly the MVN, in the setting of Vitamin B1 deficiency with preservation of vertical gaze. <b>Disclosure:</b> Dr. Chen has nothing to disclose. Dr. Warfield has nothing to disclose. Dr. Nannery has nothing to disclose. Dr. Togher has nothing to disclose. Dr. Yacoob has nothing to disclose.

Convergent innervations of mesencephalic trigeminal and vestibular nuclei neurons onto oculomotor and pre-oculomotor neurons-Tract tracing and triple labeling in rats.

In studies of vestibulo-ocular reflex (VOR), the horizontal VOR circuit is much clearer than vertical-torsional VOR. The circuit and mechanism of gravity-related vertical-torsional VOR is probably weak. "Somatosensory vestibular interaction" is a known extra source to facilitate VOR, and cervico-ocular reflex is a representative for torsional VOR compensation. Whereas, how the cervical afferents finally reach the oculomotor system is less documented. Actually, when the head tilts, which generates cervico-ocular reflex, not only the neck muscle is activated, but also the jaw muscle is stretched by gravity dragged mandible and/or tissue-muscle connection between the mandible and clavicle. We have previously identified a projection from the jaw muscle afferent mesencephalic trigeminal nucleus (Vme) neurons to oculomotor nuclei (III/IV) and their premotor neurons in interstitial nucleus of Cajal (INC)-a well-known pre-oculomotor center manipulating vertical-torsional eye movements. We hypothesized that these projections may interact with vestibulo-ocular signals during vertical-torsional VOR, because effects of gravity on jaw muscles and bones has been reported. Thus, we injected different anterograde tracers into the Vme and medial vestibular nucleus (MVN)-the subnuclear area particularly harboring excitatory vestibulo-ocular neurons, and immunostained III/IV motoneurons. Retrograde tracer was injected into the III in the same animals after dual anterograde tracers' injections. Under confocal microscope, we observed the Vme and MVN neuronal endings simultaneously terminated onto the same III/IV motoneurons and the same INC pre-oculomotor neurons. We consider that jaw muscle proprioceptive Vme neurons projecting to the III/IV and INC would sense spindle activity if the jaw muscle is stretched by gravity dragged mandible or connection between mandible and clavicle during head rolling. Therefore, the convergent innervation of the Vme and MVN neurons onto the oculomotor and pre-oculomotor nuclei would be a neuroanatomic substrate for interaction of masticatory proprioception with the vestibulo-ocular signals upon the oculomotor system during vertical-torsional VOR.

Stochastic and sinusoidal electrical stimuli increase the irregularity and gain of Type A and B medial vestibular nucleus neurons, in vitro.

Galvanic vestibular stimulation (GVS) has been shown to improve vestibular function potentially via stochastic resonance, however, it remains unknown how central vestibular nuclei process these signals. In vivo work applying electrical stimuli to the vestibular apparatus of animals has shown changes in neuronal discharge at the level of the primary vestibular afferents and hair cells. This study aimed to determine the cellular impacts of stochastic, sinusoidal, and stochastic+sinusoidal stimuli on individual medial vestibular nucleus (MVN) neurons of male and female C57BL/6 mice. All stimuli increased the irregularity of MVN neuronal discharge, while differentially affecting neuronal gain. This suggests that the heterogeneous MVN neuronal population (marked by differential expression of ion channels), may influence the impact of electrical stimuli on neuronal discharge. Neuronal subtypes showed increased variability of neuronal firing, where Type A and B neurons experienced the largest gain changes in response to stochastic and sinusoidal stimuli. Type C neurons were the least affected regarding neuronal firing variability and gain changes. The membrane potential (MP) of neurons was altered by sinusoidal and stochastic+sinusoidal stimuli, with Type B and C neuronal MP significantly affected. These results indicate that GVS-like electrical stimuli impact MVN neuronal discharge differentially, likely as a result of heterogeneous ion channel expression.

Direct projection pathway between medial vestibular nucleus and vestibular efferent neurons in rats and its electrophysiological characteristics

Objective: To confirm the direct projection pathway between the medial vestibular nucleus (MVN) and vestibular efferent (VE) neurons and explore its electrophysiological characteristics. Methods: Newborn [(9±1) day-old] male and female Wistar rats were used in the study. The postsynaptic currents of VE were recorded after stimulating neurons in MVN by the whole-cell patch clamp recording technique. The action potentials (APs) of the afferent neurons in MVN were recorded retrogradely after stimulating the area of VE neurons distribution medial to genu of facial nerve (g7), and the position and shape of the recorded neurons were determined by biocytin staining. Results: The resting membrane potentials of VE neurons located medial to g7 ranged between -70 mV and -55 mV in current clamp recordings. Excitatory postsynaptic currents (EPSCs) were recorded in the VE neurons medial to the g7 evoked by single-pulse (0.08 mA, 0.1 Hz, 100 μs) electrical stimulation of MVN. The mean values of amplitude and duration were (195.6±23.7) pA and (23.9±5.9) ms, respectively. APs were recorded in MVN after stimulating the distribution area of VE neurons. The mean amplitude of the action potentials was (62.0±4.3) mV, and the mean duration was (94.9±4.7) ms. Biocytin staining indicated that the recorded neurons located in MVN and the axons' terminals went into the area medial to g7 in which VE neurons located. Conclusions: There is a direct excitatory pathway projecting from MVN to VE neurons medial to g7. Its physiological function may be related to the feedback regulation of vestibular center to peripheral vestibular afferent signals.

Effects of Betahistine on the Development of Vestibular Compensation after Unilateral Labyrinthectomy in Rats.

Background: Vestibular compensation (VC) after unilateral labyrinthectomy (UL) consists of the initial and late processes. These processes can be evaluated based on the decline in the frequency of spontaneous nystagmus (SN) and the number of MK801-induced Fos-positive neurons in the contralateral medial vestibular nucleus (contra-MVe) in rats. Histamine H3 receptors (H3R) are reported to be involved in the development of VC. Objective: We examined the effects of betahistine, an H3R antagonist, on the initial and late processes of VC in UL rats. Methods: Betahistine dihydrochloride was continuously administered to the UL rats at doses of 100 and 200 mg/kg/day using an osmotic minipump. MK801 (1.0 mg/kg) was intraperitoneally administered on days 7, 10, 12, and 14 after UL, while Fos-positive neurons were immunohistochemically stained in the contra-MVe. Results: The SN disappeared after 42 h, and continuous infusion of betahistine did not change the decline in the frequency of SN. The number of MK801-induced Fos-positive neurons in contra-MVe significantly decreased on days 7, 10, and 12 after UL in a dose-dependent manner in the betahistine-treated rats, more so than in the saline-treated rats. Conclusion: These findings suggest that betahistine facilitated the late, but not the initial, process of VC in UL rats.

Anatomical projections to the dorsal tegmental nucleus and abducens nucleus arise from separate cell populations in the nucleus prepositus hypoglossi, but overlapping cell populations in the medial vestibular nucleus.

Specialized circuitry in the brain processes spatial information to provide a sense of direction used for navigation. The dorsal tegmental nucleus (DTN) is a core component of this circuitry and utilizes vestibular inputs to generate neural activity encoding the animal's directional heading. Projections arising from the nucleus prepositus hypoglossi (NPH) and the medial vestibular nucleus (MVe) are thought to transmit critical vestibular signals to the DTN and other brain areas, including the abducens nucleus (ABN), a component of eye movement circuitry. Here, we utilized a dual retrograde tracer approach in rats to investigate whether overlapping or distinct populations of neurons project from the NPH or MVe to the DTN and ABN. We report that individual MVe neurons project to both the DTN and ABN. In contrast, we observed individual NPH neurons that project to either the DTN or ABN, but rarely to both structures simultaneously. We also examined labeling patterns in other structures located in the brainstem and posterior cortex and observed (1) complex patterns of interhemispheric connectivity between the left and right DTN, (2) projections from the supragenual nucleus, interpeduncular nucleus, and retrosplenial cortex to the DTN, (3) projections from the lateral superior olive to the ABN, and (4) a unique population of cerebrospinal fluid-contacting neurons in the dorsal raphe nucleus. Collectively, our experiments provide valuable new information that extends our understanding of the anatomical organization of the brain's spatial processing circuitry.

The intrinsic plasticity of medial vestibular nucleus neurons during vestibular compensation\u2014a systematic review and meta-analysis

BackgroundVestibular compensation is a homeostatic process that occurs in the central nervous system in response to peripheral vestibular dysfunction. Experimental studies in rodent models have suggested that unilateral peripheral vestibular lesions are correlated with an increase in the intrinsic excitability of central vestibular neurons. This process may be dependent on the intrinsic properties of the neurons themselves. We aimed to conduct a systematic review of the literature to survey the evidence for changes in intrinsic plasticity observed during the acute phase of vestibular compensation.MethodsWe systematically reviewed the literature regarding the electrophysiological effect of experimentally induced unilateral vestibular deafferentation (UVD) on the intrinsic membrane properties of medial vestibular nucleus neurons in animal models. We developed tools to assess the methodological quality (precision, validity and bias) of studies that met pre-determined inclusion and exclusion criteria. We extracted numerical data and performed a meta-analysis of specific quantitative data pooled from these studies.ResultsWe identified 17 studies that satisfied the inclusion criteria. There is moderate quality evidence to suggest a statistically significant increase in the intrinsic excitability of medial vestibular nucleus neurons following unilateral vestibular deafferentation. Specifically, the spontaneous discharge rate increases by 4 spikes/s on average and the sensitivity to current stimuli increases.ConclusionUsing this novel approach, we demonstrate that the methodology of systematic review and meta-analysis is a useful tool in the summation of data across experimental animal studies with similar aims.

Heterogeneous vestibulocerebellar mossy fiber projections revealed by single axon reconstruction in the mouse.

A significant population of neurons in the vestibular nuclei projects to the cerebellum as mossy fibers (MFs) which are involved in the control and adaptation of posture, eye-head movements, and autonomic function. However, little is known about their axonal projection patterns. We studied the morphology of single axons of medial vestibular nucleus (MVN) neurons as well as those originating from primary afferents, by labeling with biotinylated dextran amine (BDA). MVN axons (n = 35) were classified into three types based on their major predominant termination patterns. The Cbm-type terminated only in the cerebellum (15 axons), whereas others terminated in the cerebellum and contralateral vestibular nuclei (cVN/Cbm-type, 13 axons), or in the cerebellum and ipsilateral vestibular nuclei (iVN/Cbm-type, 7 axons). Cbm- and cVN/Cbm-types mostly projected to the nodulus and uvula without any clear relationship with longitudinal stripes in these lobules. They were often bilateral, and sometimes sent branches to the flocculus and to other vermal lobules. Also, the iVN/Cbm-type projected mainly to the ipsilateral nodulus. Neurons of these types of axons showed different distribution within the MVN. The number of MF terminals of some vestibulocerebellar axons, iVN/Cbm-type axons in particular, and primary afferent axons were much smaller than observed in previously studied MF axons originating from major precerebellar nuclei and the spinal cord. The results demonstrated that a heterogeneous population of MVN neurons provided divergent MF inputs to the cerebellum. The cVN/Cbm- and iVN/Cbm-types indicate that some excitatory neuronal circuits within the vestibular nuclei supply their collaterals to the vestibulocerebellum as MFs.

Postsynaptic GluN2B-containing NMDA receptors contribute to long-term depression induction in medial vestibular nucleus neurons of juvenile rats

Medial vestibular nucleus (MVN) neurons are involved in the regulation of eye movements to endure the stability of the image during head movement, and play a critical role in plasticity of the vestibulo-ocular reflex (VOR) during the juvenile period. We have previously shown that the long-term depression (LTD) of synaptic transmission was induced by high frequency stimulation (HFS) and blocked by N-methyl-D-aspartate (NMDA) receptor antagonist D-APV at the vestibular afferent synapses of type-B MVN neurons. In the present study, we used whole-cell patch-clamp recordings in vitro to investigate the subunit composition of these NMDA receptors in the induction of LTD in MVN slices from postnatal 13–16 day rats. We found that LTD induced in type-B neurons of the rat MVN with HFS was blocked by Ro 25–6981, a specific antagonist for GluN2B-containing NMDA receptors. Moreover, the other selective GluN2B-containing NMDA receptor antagonist (ifenprodil) also prevented the induction of LTD. However, bath application of the GluN2A-containing NMDA receptor antagonists (Zn2+ and TCN 201) had no influence on the induction of LTD. Similar results were obtained by exogenously applied two GluN2C/GluN2D-preferring NMDA receptor antagonists (PPDA and UBP 141). Furthermore, presynaptic NMDA receptor subunits are not necessary for vestibular LTD. These results suggest that the induction of LTD by HFS in vestibular afferent synapses of type-B MVN neurons requires postsynaptic GluN2B-containing NMDA receptors, but not GluN2A-containing NMDA receptors or GluN2C/GluN2D-containing NMDA receptors.

Graded Coexpression of Ion Channel, Neurofilament, and Synaptic Genes in Fast-Spiking Vestibular Nucleus Neurons.

Computations that require speed and temporal precision are implemented throughout the nervous system by neurons capable of firing at very high rates, rapidly encoding and transmitting a rich amount of information, but with substantial metabolic and physical costs. For economical fast spiking and high throughput information processing, neurons need to optimize multiple biophysical properties in parallel, but the mechanisms of this coordination remain unknown. We hypothesized that coordinated gene expression may underlie the coordinated tuning of the biophysical properties required for rapid firing and signal transmission. Taking advantage of the diversity of fast-spiking cell types in the medial vestibular nucleus of mice of both sexes, we examined the relationship between gene expression, ionic currents, and neuronal firing capacity. Across excitatory and inhibitory cell types, genes encoding voltage-gated ion channels responsible for depolarizing and repolarizing the action potential were tightly coexpressed, and their absolute expression levels increased with maximal firing rate. Remarkably, this coordinated gene expression extended to neurofilaments and specific presynaptic molecules, providing a mechanism for coregulating axon caliber and transmitter release to match firing capacity. These findings suggest the presence of a module of genes, which is coexpressed in a graded manner and jointly tunes multiple biophysical properties for economical differentiation of firing capacity. The graded tuning of fast-spiking capacity by the absolute expression levels of specific ion channels provides a counterexample to the widely held assumption that cell-type-specific firing patterns can be achieved via a vast combination of different ion channels.SIGNIFICANCE STATEMENT Although essential roles of fast-spiking neurons in various neural circuits have been widely recognized, it remains unclear how neurons efficiently coordinate the multiple biophysical properties required to maintain high rates of action potential firing and transmitter release. Taking advantage of diverse fast-firing capacities among medial vestibular nucleus neurons of mice, we identify a group of ion channel, synaptic, and structural genes that exhibit mutually correlated expression levels, which covary with firing capacity. Coexpression of this fast-spiking gene module may be a basic strategy for neurons to efficiently and coordinately tune the speed of action potential generation and propagation and transmitter release at presynaptic terminals.

Ca2+-dependent recruitment of voltage-gated sodium channels underlies bilirubin-induced overexcitation and neurotoxicity

Neonatal jaundice is prevalent among newborns and can lead to severe neurological deficits, particularly sensorimotor dysfunction. Previous studies have shown that bilirubin (BIL) enhances the intrinsic excitability of central neurons and this can potentially contribute to their overexcitation, Ca2+ overload, and neurotoxicity. However, the cellular mechanisms underlying elevated neuronal excitability remain unknown. By performing patch-clamp recordings from neonatal neurons in the rat medial vestibular nucleus (MVN), a crucial relay station for locomotor and balance control, we found that BIL (3 μM) drastically increases the spontaneous firing rates by upregulating the current-mediated voltage-gated sodium channels (VGSCs), while shifting their voltage-dependent activation toward more hyperpolarized potentials. Immunofluorescence labeling and western immunoblotting with an anti-NaV1.1 antibody, revealed that BIL elevates the expression of VGSCs by promoting their recruitment to the membrane. Furthermore, we found that this VGSC-trafficking process is Ca2+ dependent because preloading MVN neurons with the Ca2+ buffer BAPTA-AM, or exocytosis inhibitor TAT-NSF700, prevents the effects of BIL, indicating the upregulated activity and density of functional VGSCs as the core mechanism accountable for the BIL-induced overexcitation of neonatal neurons. Most importantly, rectification of such overexcitation with a low dose of VGSC blocker lidocaine significantly attenuates BIL-induced cell death. We suggest that this enhancement of VGSC currents directly contributes to the vulnerability of neonatal brain to hyperbilirubinemia, implicating the activity and trafficking of NaV1.1 channels as a potential target for neuroprotection in cases of severe jaundice.

Stochastic Noise Application for the Assessment of Medial Vestibular Nucleus Neuron Sensitivity In Vitro.

Galvanic vestibular stimulation (GVS) has been shown to improve balance measures in individuals with balance or vestibular impairments. This is proposed to be due to the stochastic resonance (SR) phenomenon, which is defined as application of a low-level/subthreshold stimulus to a non-linear system to increase detection of weaker signals. However, it is still unknown how SR exhibits its positive effects on human balance. This is one of the first demonstrations of the effects of sinusoidal and stochastic noise on individual neurons. Using whole-cell patch clamp electrophysiology, sinusoidal and stochastic noise can be applied directly to individual neurons in the medial vestibular nucleus (MVN) of C57BL/6 mice. Here we demonstrate how to determine the threshold of MVN neurons in order to ensure the sinusoidal and stochastic stimuli are subthreshold and from this, determine the effects that each type of noise has on MVN neuronal gain. We show that subthreshold sinusoidal and stochastic noise can modulate the sensitivity of individual neurons in the MVN without affecting basal firing rates.

Histamine H1 Receptor Contributes to Vestibular Compensation.

Vestibular compensation is responsible for the spontaneous recovery of postural, locomotor, and oculomotor dysfunctions in patients with peripheral vestibular lesion or posterior circulation stroke. Mechanism investigation of vestibular compensation is of great importance in both facilitating recovery of vestibular function and understanding the postlesion functional plasticity in the adult CNS. Here, we report that postsynaptic histamine H1 receptor contributes greatly to facilitating vestibular compensation. The expression of H1 receptor is restrictedly increased in the ipsilesional rather than contralesional GABAergic projection neurons in the medial vestibular nucleus (MVN), one of the most important centers for vestibular compensation, in unilateral labyrinthectomized male rats. Furthermore, H1 receptor mediates an asymmetric excitation of the commissural GABAergic but not glutamatergic neurons in the ipsilesional MVN, which may help to rebalance bilateral vestibular systems and promote vestibular compensation. Selective blockage of H1 receptor in the MVN significantly retards the recovery of both static and dynamic vestibular symptoms following unilateral labyrinthectomy, and remarkably attenuates the facilitation of betahistine, whose effect has traditionally been attributed to its antagonistic action on the presynaptic H3 receptor, on vestibular compensation. These results reveal a previously unknown role for histamine H1 receptor in vestibular compensation and amelioration of vestibular motor deficits, as well as an involvement of H1 receptor in potential therapeutic effects of betahistine. The findings provide not only a new insight into the postlesion neuronal circuit plasticity and functional recovery in the CNS, but also a novel potential therapeutic target for vestibular disorders.SIGNIFICANCE STATEMENT Vestibular disorders manifest postural imbalance, nystagmus, and vertigo. Vestibular compensation is critical for facilitating recovery from vestibular disorders, and of great importance in understanding the postlesion functional plasticity in the adult CNS. Here, we show that postsynaptic H1 receptor in the medial vestibular nucleus (MVN) contributes greatly to the recovery of both static and dynamic symptoms following unilateral vestibular lesion. H1 receptor selectively mediates the asymmetric activation of commissural inhibitory system in the ipsilesional MVN and actively promotes vestibular compensation. The findings provide not only a new insight into the postlesion neuronal circuit plasticity and functional recovery of CNS, but also a novel potential therapeutic target for promoting vestibular compensation and ameliorating vestibular disorders.

Vestibular Dysfunction in Wernicke's Encephalopathy: Predominant Impairment of the Horizontal Semicircular Canals.

Wernicke's encephalopathy (WE), a metabolic disorder due to thiamine deficiency, manifests with various neurological symptoms and signs. It has been known as a cause of vestibular dysfunction. Preliminary reports have proposed predominant involvement of the horizontal semicircular canals (HSCs). To better characterize the pattern of vestibular impairment in patients with WE using quantitative video head-impulse testing and to review the literature regarding this topic. From January 2014 to December 2016, we retrospectively enrolled five cases of WE that received quantitative video-head-impulse testing (vHIT). We retrieved the clinical features from the medical records and reviewed quantitative head-impulse testing (qHIT) and caloric irrigation. Based on the gain and the number of corrective saccades, the function (normal vs. impaired) of each semicircular canal was rated. In addition, we conducted a MEDLINE and EMBASE search to identify other published cases of WE that had received qHIT. Neuro-otologic and neuro-ophthalmologic findings and vestibular testing results were extracted. A total of 17 patients (own series = 5; published cases = 12) aged 54.6 ± 11 years were included. Key neurologic findings were ataxia of stance and gait (13/13, 100%), spontaneous nystagmus (7/14, 50%), gaze-evoked nystagmus (GEN) (17/17, 100%), positive bedside head-impulse testing for the horizontal canals (16/17, 94%), and memory impairment and mental changes (6/11, 54.5%). Regarding vestibular testing, qHIT (either video based or search-coil based) documented selective bilateral horizontal canal dysfunction with normal or minimal vertical canal impairment (14/14, 100%). On caloric irrigation, bilateral horizontal canal paresis was noted in most cases (10/11, 91%). In WE, signs of both peripheral and central vestibular dysfunction (i.e., GEN, ataxia of stance and gait, abnormal head-impulse testing) were common. Selective or predominant impairment of the HSCs seems to be the most common finding of WE likely related to enhanced vulnerability of the medial vestibular nuclei neurons to thiamine deficiency. Quantitative vHIT of all six semicircular canals is therefore a useful tool for the diagnosis and should be applied in all patients with suspected WE.

Effect of acupuncture at three different acupoints on electrical activity of gastric distention-affected neurons in rat medial vestibular nucleus

OBJECTIVETo observe the effect of gastric distention (GD) and acupuncture at three different acupoints on the spontaneous discharge of neurons in the medial vestibular nucleus (MVN), and to clarify the specific function of the MVN in the central integration mechanism underlying acupuncture regulation. METHODSGD was conducted using a balloon inserted in the stomach cavity, and acupuncture was performed separately at each of three acupoints: Zusanli (ST 36), Quchi (LI 11), and Weishu (BL 21). The effect of acupuncture and GD on the spontaneous discharge of MVN neurons was assessed using a glass microelectrode filled with a sodium acetate electrolyte solution containing 1% pontamine sky blue; the discharge signals from the neurons were amplified by the microelectrode amplifier and recorded in the Spike2 system. RESULTSGD and acupuncture significantly affected the spontaneous discharge of MVN neurons. Furthermore, acupuncture at Zusanli (ST 36) and Weishu (BL 21) was significantly more effective at altering the discharge of GD-responsive MVN neurons compared with GD-nonresponsive neurons. CONCLUSIONGD and acupuncture at three different acupoints affected the electrical activity of MVN neurons. The MVN is involved in the central integration mechanism underlying acupuncture regulation of gastric functions. The effects of acupuncture on gastric function may therefore be mediated via these particular MVN neurons.

Activation of 5-HT7 receptors reverses NMDA-R-dependent LTD by activating PKA in medial vestibular neurons

The medial vestibular nucleus (MVN) is a major output station for neurons that project to the vestibulo-spinal pathway. MVN neurons show capacity for long-term depression (LTD) during the juvenile period. We investigated LTD of MVN neurons using whole-cell patch-clamp recordings. High frequency stimulation (HFS) robustly induced LTD in 90% of type B neurons in the MVN, while only 10% of type A neurons were responsive, indicating that type B neurons are the major contributors to LTD in the MVN. The neuromodulator serotonin (5-HT) is known to modulate LTD in neural circuits of the cerebral cortex and the hippocampus. We therefore aim to determine the action of 5-HT on the LTD of type B MVN neurons and elucidate the relevant 5-HT receptor subtypes responsible for its action. Using specific agonists and antagonists of 5-HT receptors, we found that selective activation of 5-HT7 receptor in type B neurons in the MVN of juvenile (P13-16) rats completely abolished NMDA-receptor-mediated LTD in a protein kinase A (PKA)-dependent manner. Our finding that 5-HT restricts plasticity of type B MVN neurons via 5-HT7 receptors offers a mechanism whereby vestibular tuning contributes to the maturation of the vestibulo-spinal circuit and highlights the role of 5-HT in postural control.

Distribution and Structure of Synapses on Medial Vestibular Nuclear Neurons Targeted by Cerebellar Flocculus Purkinje Cells and Vestibular Nerve in Mice: Light and Electron Microscopy Studies.

Adaptations of vestibulo-ocular and optokinetic response eye movements have been studied as an experimental model of cerebellum-dependent motor learning. Several previous physiological and pharmacological studies have consistently suggested that the cerebellar flocculus (FL) Purkinje cells (P-cells) and the medial vestibular nucleus (MVN) neurons targeted by FL (FL-targeted MVN neurons) may respectively maintain the memory traces of short- and long-term adaptation. To study the basic structures of the FL-MVN synapses by light microscopy (LM) and electron microscopy (EM), we injected green florescence protein (GFP)-expressing lentivirus into FL to anterogradely label the FL P-cell axons in C57BL/6J mice. The FL P-cell axonal boutons were distributed in the magnocellular MVN and in the border region of parvocellular MVN and prepositus hypoglossi (PrH). In the magnocellular MVN, the FL-P cell axons mainly terminated on somata and proximal dendrites. On the other hand, in the parvocellular MVN/PrH, the FL P-cell axonal synaptic boutons mainly terminated on the relatively small-diameter (< 1 μm) distal dendrites of MVN neurons, forming symmetrical synapses. The majority of such parvocellular MVN/PrH neurons were determined to be glutamatergic by immunocytochemistry and in-situ hybridization of GFP expressing transgenic mice. To further examine the spatial relationship between the synapses of FL P-cells and those of vestibular nerve on the neurons of the parvocellular MVN/PrH, we added injections of biotinylated dextran amine into the semicircular canal and anterogradely labeled vestibular nerve axons in some mice. The MVN dendrites receiving the FL P-cell axonal synaptic boutons often closely apposed vestibular nerve synaptic boutons in both LM and EM studies. Such a partial overlap of synaptic boutons of FL P-cell axons with those of vestibular nerve axons in the distal dendrites of MVN neurons suggests that inhibitory synapses of FL P-cells may influence the function of neighboring excitatory synapses of vestibular nerve in the parvocellular MVN/PrH neurons.

Expression of glycine receptors and gephyrin in rat medial vestibular nuclei and flocculi following unilateral labyrinthectomy.

The medial vestibular nucleus (MVN) and the cerebellar flocculus have been known to be the key areas involved in vestibular compensation (VC) following unilateral labyrinthectomy (UL). In this study, we examined the role of gephyrin and glycine receptor (GlyR) in VC using Sprague-Dawley rats, in an aim to gain deeper insight into the mechanisms responsible for VC. The expression of the α1 and β subunits of GlyR and gephyrin was immunohistochemically localized in rat MVN and flocculi. The mRNA and protein expression of GlyR (α1 and β subunits) and gephyrin was quantitatively determined by RT-qPCR and western blot analysis at 8 h, and at 1, 3 and 7 days following UL. It was found that in the ipsilateral MVN, the mRNA and protein expression of the β subunit of GlyR was significantly increased in comparison to the sham-operated (P<0.01) rats, and in comparison to the contralateral side (P<0.01) at 8 h following UL. In the ipsilateral flocculi, GlyR β protein expression was significantly elevated (P<0.01 for all), as compared to the sham-operated rats at 8 h, and at 1 and 3 days and to the contralateral side 8 h, 1 and 3 days following UL. No significant differences were observed in the mRNA and protein expression of GlyR α1 and gephyrin in the MVN or flocculi between the two sides (ipsilateral and contralateral) in the UL group, and between the sham-operated group and the UL group at any time point. The findings of our study thus suggest that GlyR plays a major role in the recovery of the resting discharge of the deafferented MVN neurons in the central vestibular system.

Quantitative evaluations of the contribution of the excitatory ionic conductance to repetitive spiking in a mathematical model of medial vestibular nucleus neurons.

Medial vestibular nucleus neurons show spontaneous repetitive spiking. This spiking activity was reproduced by a Hodgkin-Huxley-type mathematical model, which was developed in a previous study. The present study performed computer simulations of this model to evaluate the contribution of the excitatory ionic conductance to repetitive spiking. The present results revealed the difference in the influence of the transient sodium, persistent sodium, and calcium conductance on spiking activity. The differences between the present and previous results obtained from other neuronal mathematical models were discussed.