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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]

• 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]

• 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]