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• Kennedy patients exhibit severe balance deficits in conditions of absent vision. • Horizontal vestibulo-ocular reflex function is preserved. • The balance impairment stems from a diminished somatosensory input. • Some Kennedy patients face difficulties in producing fast eye movements. Spinal and bulbar muscular atrophy (Kennedy's disease) has been associated with balance dysfunction and falls. However, postural control has not been studied quantitatively. Here, we quantified upright stance and aimed to disentangle the role of vestibular, proprioceptive and oculomotor deficits. Static balance was assessed in Kennedy patients (n = 7) during quiet stance on a force platform under different visual and proprioceptive feedback conditions. Vestibular function was assessed with the video head impulse test. Sural nerve neurography was employed to evaluate the severity of peripheral neuropathy. Also, horizontal saccades were recorded and quantified by the main sequence relationship. Posturographic analyses revealed significantly increased body sway, more pronounced in conditions with closed eyes, which was also reflected in the calculated Romberg indices. Horizontal vestibulo-ocular reflex gains were normal, i.e. > 0.75. In contrast, compound sensory nerve action potentials were markedly decreased in all patients (mean = 2.4 μV). Two patients showed slow saccades with increased exponential main sequence constants. We conclude that Kennedy patients exhibit severe deficits in quiet stance. Postural instability is greatest in conditions of absent vision with reduced proprioception being the main determinant of unsteadiness. Some patients show slowed saccadic eye movements suggesting a nuclear abducens neuronopathy. [ABSTRACT FROM AUTHOR]

Highlights • Surgery-free VOR measurement that allows screen for genes and drugs affecting vestibular function has been enabled. • Daily-progression profile of the vestibular impairment caused by IDPN at different dose levels has been obtained. • Mice with homozygous mutations of Lhfpl5 and Cdh23 have been identified based on their reduced VOR-response levels. Abstract Vestibulo-ocular reflex (VOR) responding to acceleration stimuli is originated from the vestibular apparatuses and thus widely used as an in vivo indicator of the vestibular function. We have developed a vestibular function testing (VFT) system that allows to evaluate VOR response with improved efficiency. The previously required surgical procedure has been avoided by using a newly designed animal-immobility setup. The efficacy of our VFT system was demonstrated on the mice with vestibular abnormalities caused by either genetic mutations (Lhfpl5−/− or Cdh23−/−) or applied vestibulotoxicant (3,3′-iminodipropionitrile, IDPN). Daily longitudinal inspection of the VOR response in the IDPN-administered mice gives the first VOR-based daily-progression profile of the vestibular impairment. The capability of VOR in quantifying the severity of toxicant-induced vestibular deficits has been also demonstrated. The acquired VOR-measurement results were validated against the corresponding behavioral-test results. Further validation against immunofluorescence microscopy was applied to the VOR data obtained from the IDPN-administered mice. We conclude that the improved efficiency of our surgery-free VFT system, firstly, enables the characterization of VOR temporal dynamics and quantification of vestibular-impairment severity that may reveal useful information in toxicological and/or pharmaceutical studies; and, secondly, confers our system promising potential to serve as a high-throughput screener for identifying genes and drugs that affect vestibular function. [ABSTRACT FROM AUTHOR]

Background Parkinson’s disease (PD) is a common neurodegenerative disease characterized by dopaminergic neuronal loss. The underlying cause of PD is unknown. Objective To assess the clinical relevance of vestibular-ocular reflex (VOR) gain in patients with PD, especially those in the early stages. Methods Sixty-three PD patients and 56 control healthy individuals were enrolled in this study between Mar 2015 and Aug 2015. VOR gains were determined by video head impulse test (vHIT) device. Statistical analysis was performed to assess the difference in VOR gains between PD patients and normal people. The relationship of VOR gain with age, duration and severity of disease was also assessed. Results In the control group, average VOR gain was 0.98 ± 0.09 on the left side and 0.99 ± 0.16 on the right side. No statistically significant difference was observed between the two sides in the control group ( P > 0.05). In the PD group, average VOR gain was 1.20 ± 0.22 on the left side and 1.23 ± 0.23 on the right side. No statistically significant difference was observed between the two sides in the PD group ( P > 0.05). There was a significant difference in VOR gain between the PD (both in early and mid-late stages) and the control group ( P < 0.05). A weak correlation was observed between VOR gain and the motor Unified Parkinson Disease Rating Scale score. No correlation of VOR gain with age, duration of disease or the Hoehn and Yahr Scale score was observed. VOR gains in PD patients were found to be higher than normal, especially in the early stages of the disease. Conclusion vHIT is a potential tool to determine the VOR gain in PD patients and may help detect PD at an early stage. [ABSTRACT FROM AUTHOR]

Two characteristics of otolith-ocular responses – linear vestibulo-ocular reflex and vergence – were examined during constant velocity off-vertical axis rotation (OVAR) in the dark. Sixteen subjects were rotated about their longitudinal axis when tilted 30° relative to the direction of gravity. Rotational velocities were 36 and 288/s corresponding to frequencies of 0.1 and 0.8 Hz, respectively. Subjects were asked to imagine stationary targets located at 0.5 m, 1 m, and 2 m in the straight-ahead direction. Binocular eye movements were recorded in the dark using infrared videography. The modulation of horizontal slow phase velocity during OVAR was larger at 0.8 Hz than at 0.1 Hz, and the modulation at the high frequency was larger for the near target than for the mid and far targets. These characteristics confirm that the horizontal slow phase velocity during yaw OVAR represents a translational otolith-ocular reflex in response to acceleration along the inter-aural axis that is dependent on imagined fixation distance. [ABSTRACT FROM AUTHOR]

Sudden unilateral loss of vestibular afferent input causes nystagmus, ocular misalignment, postural instability and vertigo, all of which improve significantly over the first few days after injury through a process called vestibular compensation (VC). Efferent neuronal signals to the labyrinth are thought to be required for VC. To better understand efferent contributions to VC, we compared the time course of VC in wild-type (WT) mice and α9 knockout (α9 −/− ) mice, the latter lacking the α9 subunit of nicotinic acetylcholine receptors (nAChRs), which is thought to represent one signaling arm activated by the efferent vestibular system (EVS). Specifically, we investigated the time course of changes in the fast/direct and slow/indirect components of the angular vestibulo-ocular reflex (VOR) before and after unilateral labyrinthectomy (UL). Eye movements were recorded using infrared video oculography in darkness with the animal stationary and during sinusoidal (50 and 100°/s, 0.5–5 Hz) and velocity step (150°/s for 7–10 s, peak acceleration 3000°/s 2 ) passive whole-body rotations about an Earth-vertical axis. Eye movements were measured before and 0.5, 2, 4, 6 and 9 days after UL. Before UL, we found frequency- and velocity-dependent differences between WT and α9 −/− mice in generation of VOR quick phases. The VOR slow phase time constant (TC) during velocity steps, which quantifies contributions of the indirect component of the VOR, was longer in α9 −/− mutants relative to WT mice. After UL, spontaneous nystagmus (SN) was suppressed significantly earlier in WT mice than in α9 −/− mice, but mutants achieved greater recovery of TC symmetry and VOR quick phases. These data suggest (1) there are significant differences in vestibular and oculomotor functions between these two types of mice, and (2) efferent signals mediated by α9 nicotinic AChRs play a role during VC after UL. [ABSTRACT FROM AUTHOR]

Highlights: [•] Time interval between velocity steps influences vestibular habituation of nystagmus. [•] VOR habituates only when steps are delivered after the primary phase nystagmus. [•] Perception of self-rotation habituates irrespectively of stimulus interval. [Copyright &y& Elsevier]

Highlights: [•] BPF of 1–1000Hz showed larger oVEMP amplitude than BPF of 10–1000Hz and BPF of 100–1000Hz. [•] BPF of 1–1000Hz did not significantly differ in oVEMPs from BPF of 1–500Hz and BPF of 1–2000Hz. [•] The optimal BPF setting for acoustic stimuli in recording oVEMP is suggested between 1 and 1000Hz. [ABSTRACT FROM AUTHOR]

Abstract: Topical FGLM-NH2 (Phenylalanine–Glycine–Leucine–Methionine–Amide) plus SSSR (Serine–Serine–Serine–Arginine) facilitates recovery from vestibular disorders induced by (±)-α-amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid (AMPA) in guinea pigs and might offer a treatment strategy for patients with peripheral vestibular disorders. The tetrapeptide FGLM-NH2 derived from substance P (SP) can be used to treat corneal disorders when combined with SSSR, which is a tetrapeptide derived from insulin-like growth factor-1 (IGF-1). We examined the influence of FGLM-NH2 plus SSSR when locally applied to the unilateral inner ear of guinea pigs with vestibular disorder induced by AMPA. A total of 18 Hartley white guinea pigs were assigned to groups receiving either FGLM-NH2 plus SSSR, artificial perilymph, or no treatment at all. A hole was drilled adjacent to the round window, with AMPA then infused into the hole in order to induce the vestibular disorder. Thereafter, FGLM-NH2 plus SSSR or artificial perilymph was delivered via an osmotic pump that was inserted into the hole. Sinusoidal rotation tests were used for observing spontaneous nystagmus and for measurements of the vestibulo-ocular reflexes (VOR). Two animals from each group were immunohistochemically examined at 24h after the treatment. Spontaneous nystagmus decreased immediately after FGLM-NH2 plus SSSR infusion. The recovery of the VOR gains was statistically faster than that seen in the control group at 3 and 7 days after treatment. Immunohistochemical examination revealed that many synaptic ribbons, which are markers of the synapse, were stained in the FGLM-NH2 plus SSSR group compared with the untreated group. Topical application of FGLM-NH2 plus SSSR accelerates functional recovery from AMPA-induced vestibular disorders by facilitating synaptic regeneration in guinea pigs. [Copyright &y& Elsevier]

Abstract: The vestibulo-ocular reflex (VOR) was studied to examine the utility of off-vertical axis rotation (OVAR) in the diagnosis of acoustic neurinoma. Subjects were sinusoidally rotated with eyes open in complete darkness at frequencies of 0.4 and 0.8Hz with a maximum angular velocity of 60°/s at either earth-vertical axis rotation (EVAR) or OVAR. Thirteen patients with acoustic neurinomas were investigated. Results showed that VOR gain during OVAR at 0.8Hz and in a 30° nose-up position in patients with internal auditory canal tumors was significantly less than the gain measured during EVAR. The VOR gain measured from all patients (including those with tumors extending to the cerebellopontine angle) was not significantly different when the patients were subjected to EVAR and OVAR. These observations were possibly due to superior vestibular nerve dysfunction. We concluded that certain stimulating parameters—patient''s nose tilted up 30°; sinusoidal OVAR at 0.8Hz and 60°/s maximum angular head velocity—were useful for evaluating vestibular function in patients suffering from an acoustic neurinoma located within the internal auditory canal. [Copyright &y& Elsevier]

Abstract: Previous studies have reported localization of substance P (SP) within the inner ear and that SP exists abundantly within vestibular endorgans. While SP''s functional role in the inner ear remains unclear, SP can act as a neuromodulator in the CNS and directly influences neuronal excitability. We hypothesized that SP might influence neuronal excitability within the vestibular periphery. The present study used the sinusoidal rotation test to investigate the influence of SP after its local application in the guinea pig unilateral inner ear. A tiny hole was made adjacent to the round window in the right ears of Hartley white guinea pigs that had normal tympanic membranes and Preyer reflexes. An osmotic pump infused SP (10−4 M, 10−3 M, and 10−2 M), neurokinin-1 (NK-1) receptor antagonist (10−3 M) alone, or SP (10−3 M)+NK-1 receptor antagonist (10−3 M) through this hole, with rotation tests performed before, and 12h and 24h after the treatment. Results were used to calculate the vestibulo-ocular reflex (VOR) gains. After administration of 10−3 M and 10−2 M SP, significant increases in the VOR gains were noted at 12h after treatment, with these gains disappearing by 24h after treatment. This increase was not observed when there was simultaneous NK-1 receptor antagonist administration. There were also no changes in the VOR gains noted after administration of 10−4 M SP or the NK-1 receptor antagonist alone. These results indicate the possibility that SP may act on vestibular endorgans as an excitatory factor via the NK-1 receptors. [Copyright &y& Elsevier]

Abstract: Mechanoreceptive hair-cells of the vertebrate inner ear have a remarkable sensitivity to displacement, whether excited by sound, whole-body acceleration or substrate-borne vibration. In response to seismic or substrate-borne vibration, thresholds for vestibular afferent fibre activation have been reported in anamniotes (fish and frogs) in the range −120 to −90dB re 1 g. In this article, we demonstrate for the first time that the human vestibular system is also extremely sensitive to low-frequency and infrasound vibrations by making use of a new technique for measuring vestibular activation, via the vestibulo-ocular reflex (VOR). We found a highly tuned response to whole-head vibration in the transmastoid plane with a best frequency of about 100Hz. At the best frequency we obtained VOR responses at intensities of less than −70dB re 1 g, which was 15dB lower than the threshold of hearing for bone-conducted sound in humans at this frequency. Given the likely synaptic attenuation of the VOR pathway, human receptor sensitivity is probably an order of magnitude lower, thus approaching the seismic sensitivity of the frog ear. These results extend our knowledge of vibration-sensitivity of vestibular afferents but also are remarkable as they indicate that the seismic sensitivity of the human vestibular system exceeds that of the cochlea for low-frequencies. [Copyright &y& Elsevier]

• Zebrafish motor activity varies in antiphase with sinusoidally-modulated light. • Mean swimming speed is inversely related to illuminance by a power function. • Motor activity is also influenced by the proportional rate of change of illuminance. • The motor response to illuminance is dependent on dopaminergic function. • The illuminance-activity assay may provide a useful 96-well screening tool. Larval zebrafish show stereotyped motor responses to changes in ambient illumination. The responses can be evaluated in 96-well plates, and are used widely to assess neurological function in zebrafish models. However, the square-wave (on/off) light stimuli commonly employed in these studies do not allow analysis of the relationship between motor activity and illumination intensity or its rate of change. To address this limitation, we measured larval zebrafish motor function while ambient illumination was modulated sinusoidally. Motor activity varied robustly and reproducibly in antiphase with illumination. The relationship between mean swimming speed (dependent variable) and illuminance (independent variable) was described most closely by a power function, and was influenced dynamically by the proportional rate of change of illuminance. Several predictions from this model were verified experimentally by testing responses to sinusoidal illumination waveforms that were amplitude-, phase-, or offset-modulated, or transformed by a power function. At concentrations ≤5 μM, the dopamine D2 receptor inverse agonist haloperidol selectively abrogated the motor response to decreasing Illuminance without altering baseline activity in bright light, suggesting that dopamine is essential for illuminance-dependent motor function. These data contribute to understanding the environmental determinants of motor activity in zebrafish larvae, suggest experimental opportunities to elucidate underlying neural mechanisms, and potentially provide an assay of dopaminergic function for chemical and genetic screening applications. [ABSTRACT FROM AUTHOR]

Abstract: The vestibulo-ocular reflex (VOR) was studied via sinusoidal off-vertical axis rotation (OVAR) to evaluate otolith function in patients with benign paroxysmal positional vertigo (BPPV). Subjects were sinusoidally rotated with eyes open in complete darkness at frequencies of 0.4 and 0.8Hz with a maximum angular velocity of 60°/s in earth vertical axis rotation (EVAR) and OVAR. Ten patients with BPPV patients were investigated. We performed OVAR tests for all patients for the following different points and compared otolith function: (1) The point at which patients had typical nystagmus; we call this state ‘Before’, that is, before recovery. (2) The point when their nystagmus disappeared; we call this state ‘After’ that is, after nystagmus disappear. Results showed that VOR gain during OVAR at 0.8Hz in a 30° nose-up position in BPPV patients was significantly less than the gain during EVAR at the point Before. On the other hand, gain was not significantly different between EVAR and OVAR at the point After. VOR gain itself at 0.8Hz nose-up OVAR showed a significant increase at the point After compared to Before. This increase of VOR gain might be caused by the recovery of the otolith function in patients with BPPV. [Copyright &y& Elsevier]

Abstract: The vestibulo-ocular reflex (VOR) was studied via sinusoidal off-vertical axis rotation (OVAR) to evaluate the otolith function in patients with benign paroxysmal positional vertigo (BPPV). Subjects were sinusoidally rotated with eyes open in complete darkness at frequencies of 0.4 and 0.8Hz with a maximum angular velocity of 60°s−1 in earth-vertical axis rotation (EVAR) and OVAR. Twenty-three controls and 24 BPPV patients were investigated. Results showed that VOR gain during OVAR at 0.8Hz in a 30° nose-up position in BPPV patients was significantly less than the gain during EVAR, whereas the gain was not significantly different between EVAR and OVAR in the controls in each condition. In addition, to examine each type of BPPV, we also investigated whether there were any differences between the patients who suffered from dizziness and those who did not. VOR gain in OVAR of BPPV patients who were suffering from dizziness was significantly less than that of BPPV patients without dizziness. Not only cupulolithiasis or canalolithiasis, but also otolith dysfunction was considered to be the possible origin of BPPV. Because sinusoidal OVAR produced minimal nausea compared to constant velocity OVAR, the stimulation of 0.8Hz nose-up in sinusoidal OVAR may be used to evaluate otolith function without discomfort for patients. [Copyright &y& Elsevier]

Abstract: This paper describes a method for achieving a peripheral vestibular blockade in rats by instillation of local anaesthetics over the round window membrane through a permanently implanted cannula. Being rapidly reversible, the effect of the anaesthetic drug is easily controlled by a single continuous infusion, which can be repeated at any time. The method offers a unique opportunity to study the consequence of single or repeated transient vestibular loss without any use of general anaesthetics, which may be a severe confounding factor. Such studies might shed light on balance disorders related to permanent vestibular loss or episodic vestibular dysfunction. To evaluate the method, spontaneous horizontal eye movements were recorded during the first 4h of continuous infusion. Unilateral infusion of ropivacaine gave rise to a high-frequency spontaneous nystagmus, reaching levels that have not been documented after a surgical labyrinthectomy under general anaesthesia. This vestibulo-oculomotor behaviour is consistent with a previous report using a single intratympanic instillation of lidocaine to achieve a short-lasting vestibular blockade. In the present study, it was demonstrated that the initial high-frequency nystagmus decreased during the first 100min of infusion before stabilizing at the same level as recorded when the effect of general anaesthesia has worn off after a surgical ablation. When the transient vestibular blockade was repeated by a second infusion during the following day, the nystagmus frequency saturated on a significantly lower level than during the first blockade. Also, serial single infusions, with recovery between each functional vestibular loss, gave rise to a less severe nystagmus. It is suggested that this phenomenon is an expression of the behavioural concept of ‘vestibular habituation’, the neural substrate of which is rather unknown. [Copyright &y& Elsevier]

The human vestibulo-ocular reflex (VOR) was investigated during active head movements in yaw while subjects were asked to view targets located at 20, 30, 40, 60, 90, and 120 cm distance aligned with eye level. Binocular video cameras were used to study conjugate eye movements and binocular convergence. Perceived target distance was determined during head oscillation by having the subjects move a cursor to the remembered position of the previously seen targets. The changes in VOR gain with viewing distance were found to be more closely related to perceived target distance than to actual target distance or fixation distance. This result suggests that the adjustment of VOR gain with viewing distance is under stronger cognitive control than would be expected of a simple motor reflex. [Copyright &y& Elsevier]

Vestibular information decreases in sensitivity with ageing, and its role becomes less important in the regulation of postural control. In addition, the practice of physical activity (PA) helps to improve vestibular sensitivity. This study aimed to evaluate PA-related benefit on vestibular function in 36 subjects split into four groups according to the period of practice. Caloric and rotatory vestibular testings showed that the performance of subjects who had begun practising PA recently were close to those of subjects active for a long time, whereas those of subjects who had stopped practising at an early age were close to those of inactive subjects. Although starting to practise PA has immediate beneficial effects on the vestibule, in terms of vestibular stimulation mechanisms these effects soon disappear if this activity is stopped. [Copyright &y& Elsevier]

The interaction of smooth pursuit eye movements, vestibulo-ocular reflex (VOR) and optokinetic reflex (OKR) is still not well understood. We therefore measured in macaque monkeys horizontal eye movements using transient horizontal rotations of a visual target, of monkeys‘ heads and/or of an optokinetic background pattern (ten combinations; smoothed position ramps of 16°). With intermediate peak velocity of target motion (vmax=12.8 °/s), pursuit held the eyes rather well on target, almost independent of concurrent vestibular or optokinetic stimuli (pursuit gain, 0.73–0.91). With vmax=1.6 °/s, in contrast, pursuit gain became strongly modified by the optokinetic stimulus. With vmax=51.2 °/s, pursuit gain became modified by vestibular stimulation. Although not intuitive, the experimental data can be explained by linear interaction (summation) of the neural driving signals for pursuit, VOR and OKR, as ascertained by simulations of a dynamic model. [Copyright &y& Elsevier]

The present study investigated vestibulo-ocular reflex (VOR), optokinetic reflex (OKR) and postural function in patients with rheumatoid arthritis (RA). Compared with controls, no differences in gaze-holding, VOR gain or phase, OKR slow phase velocity (SPV) or quick phase amplitude, optokinetic afternystagmus SPV or duration, or latency to the illusion of circularvection, were found. RA patients did exhibit greater sway in the leftward direction (P<0.01), however, this was no greater in the conditions of the Clinical Test of Sensory Interaction and Balance that increase reliance upon vestibular information. We conclude that RA patients do not exhibit substantial deficits in visual–vestibular function. [Copyright &y& Elsevier]

Abstract: To evaluate the influence of somatosensory input on the vestibulo-ocular reflex (VOR), we used sinusoidal rotation tests in 19 young, healthy volunteers. For the control condition, subjects were sinusoidally rotated in complete darkness and with eyes opened at a frequency of 0.2Hz with a maximum angular velocity of 30°/s for 30s, and at frequencies of 0.4 and 0.8Hz with a maximum angular velocity of 60°/s for 30s. Sinusoidal tests were performed at earth vertical axis rotation (EVAR). For the experimental condition, we introduced somatosensory stimulation as subjects were sinusoidally rotated at the control parameters. Subjects were told to grasp an earth-fixed metallic bar with their right hands. Thus, their right arms continued to move as the rotating chair apparatus moved. We observed a significant increment (34%) in VOR gain change only at 0.2Hz EVAR when subjects held the bar compared to that of the controls, who did not hold the bar. Gain change did not differ significantly across the other conditions. We hypothesize that arthrokinetic input (i.e., arm movement) had an additive effect on VOR in this study. This input might relate to a low-frequency component that strongly enhances the velocity storage system. Our findings have applications to types of vestibular rehabilitation regimens that implement somatosensory input. [Copyright &y& Elsevier]

• The vestibular reflexes and evoked potentials are in vivo tools for objectively assessing the vestibular function. • The VOR is widely used due to its stereotypical input-output relationship and simple motion pattern of the ocular response. • The cVEMPs and oVEMPs are able to respectively assess the saccular and utricular functions. • The VEMPs evoked by the air-conducted sound can evaluate the unilateral vestibular function noninvasively. • Location-specific functional information can be obtained by analyzing the morphological features of the VsEP waveforms. The normal function of the vestibular system is crucial for the sense of balance. The techniques used to assess the vestibular function plays a vital role in the research of the vestibular system. In this article, we have systematically reviewed some popular methods employing vestibular reflexes and vestibular evoked potentials for assessing the vestibular function in rodent models. These vestibular reflexes and vestibular evoked potentials to effective stimuli have been used as nondestructive and objective functional measures. The main types of vestibular reflexes include the vestibulo-ocular reflex (VOR), vestibulocollic reflex (VCR), and vestibulo-sympathetic reflex (VSR). They are all capable of indicating the functions of the semicircular canals and otoliths. However, the VOR assessment is much more prevalently used because of the relatively stereotypical inputoutput relationship and simple motion pattern of the ocular response. In contrast, the complicated motion pattern and small gain of the VCR response, as well as the undesired component possibly contributed from the acceleration receptors outside the labyrinths in the VSR response, restrict the widespread applications of VCR and VSR in the assessment of the vestibular system. The vestibular evoked myogenic potentials (VEMPs) and vestibular sensory evoked potentials (VsEPs) are the two typical evoked potentials that have been also employed for evaluating the vestibular function. Through exploiting different types of the VEMPs, the saccular and utricular functions can be evaluated separately. The sound-induced VEMPs, moreover, are capable of noninvasively assessing the unilateral vestibular function. The VsEPs, via the morphology of their signal waveforms, enable the access to the location-specific information that indicates the functional statuses of different components within the vestibular neural pathway. [ABSTRACT FROM AUTHOR]

• Vestibular LTD was induced by HFS in type B MVN neurons. • LTD induction depends on GluN2B-containing NMDA receptors. • GluN2A and GluN2C/GluN2D subunits are not required for LTD induction. • Presynaptic NMDA receptor subunits are not necessary for vestibular LTD. 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. [ABSTRACT FROM AUTHOR]