Vestibular Primary Afferent Neurons Research Articles

Vestibular Testing-New Physiological Results for the Optimization of Clinical VEMP Stimuli.

Both auditory and vestibular primary afferent neurons can be activated by sound and vibration. This review relates the differences between them to the different receptor/synaptic mechanisms of the two systems, as shown by indicators of peripheral function-cochlear and vestibular compound action potentials (cCAPs and vCAPs)-to click stimulation as recorded in animal studies. Sound- and vibration-sensitive type 1 receptors at the striola of the utricular macula are enveloped by the unique calyx afferent ending, which has three modes of synaptic transmission. Glutamate is the transmitter for both cochlear and vestibular primary afferents; however, blocking glutamate transmission has very little effect on vCAPs but greatly reduces cCAPs. We suggest that the ultrafast non-quantal synaptic mechanism called resistive coupling is the cause of the short latency vestibular afferent responses and related results-failure of transmitter blockade, masking, and temporal precision. This "ultrafast" non-quantal transmission is effectively electrical coupling that is dependent on the membrane potentials of the calyx and the type 1 receptor. The major clinical implication is that decreasing stimulus rise time increases vCAP response, corresponding to the increased VEMP response in human subjects. Short rise times are optimal in human clinical VEMP testing, whereas long rise times are mandatory for audiometric threshold testing.

Nociceptin/orphanin FQ peptide receptor mediates inhibition of N-type calcium currents in vestibular afferent neurons of the rat.

The vestibular system is modulated by various neuromodulators including opioid peptides. The current study was conducted to determine whether activation of nociceptin/orphanin FQ peptide (NOP) receptors modulates voltage-gated calcium currents and action potential discharge of rat vestibular afferent neurons. We performed whole cell patch-clamp recordings on cultured vestibular afferent neurons from P7-P10 Long-Evans rats. Application of nociceptin/orphanin FQ (N/OFQ), a 17-amino acid neuropeptide that is the endogenous ligand for NOP receptor, inhibits the high-voltage activated (HVA) component of the calcium current in a concentration-dependent manner with a half inhibitory concentration of 26 nM. Said inhibitory action on the calcium current is voltage-dependent, which was made clear by the fact that it was reverted in 80% by a depolarizing prepulse. Furthermore, the effect of N/OFQ was blocked by application of the specific NOP-antagonist UFP101, by preincubation with G-protein blocker pertussis toxin, and by coapplication of the specific N-type calcium-current blocker ω-conotoxin-MVIIA. N/OFQ application causes an increase in the duration and maximum rate of repolarization of action potentials. It also decreases repetitive discharge and discharge elicited by sinusoidal stimulation. These results show that in vestibular afferents, NOP receptor activation inhibits N-type calcium current by activating G proteins, mostly through the Gβγ subunit. This suggests that NOP activation produces a presynaptic modulation of primary vestibular afferent neurons' output into the vestibular nuclei, thus taking part in the integration and gain setting of vestibular information in second-order vestibular nucleus neurons.NEW & NOTEWORTHY Our results show that in primary vestibular afferent neurons, activation of the nociceptin/orphanin FQ peptide receptor inhibits the N-type calcium current by a mechanism mediated by G proteins. We propose that calcium current inhibition modulates neurotransmitter release from vestibular afferents, producing a presynaptic modulation of vestibular input to vestibular nuclei, thus contributing to gain control in the vestibular afferent input.

Regional and Developmental Differences in Na+ Currents in Vestibular Primary Afferent Neurons.

The vestibular system relays information about head position via afferent nerve fibers to the brain in the form of action potentials. Voltage-gated Na+ channels in vestibular afferents drive the initiation and propagation of action potentials, but their expression during postnatal development and their contributions to firing in diverse mature afferent populations are unknown. Electrophysiological techniques were used to determine Na+ channel subunit types in vestibular calyx-bearing afferents at different stages of postnatal development. We used whole cell patch clamp recordings in thin slices of gerbil crista neuroepithelium to investigate Na+ channels and firing patterns in central zone (CZ) and peripheral zone (PZ) afferents. PZ afferents are exclusively dimorphic, innervating type I and type II hair cells, whereas CZ afferents can form dimorphs or calyx-only terminals which innervate type I hair cells alone. All afferents expressed tetrodotoxin (TTX)-sensitive Na+ currents, but TTX-sensitivity varied with age. During the fourth postnatal week, 200–300 nM TTX completely blocked sodium currents in PZ and CZ calyces. By contrast, in immature calyces [postnatal day (P) 5–11], a small component of peak sodium current remained in 200 nM TTX. Application of 1 μM TTX, or Jingzhaotoxin-III plus 200 nM TTX, abolished sodium current in immature calyces, suggesting the transient expression of voltage-gated sodium channel 1.5 (Nav1.5) during development. A similar TTX-insensitive current was found in early postnatal crista hair cells (P5–9) and constituted approximately one third of the total sodium current. The Nav1.6 channel blocker, 4,9-anhydrotetrodotoxin, reduced a component of sodium current in immature and mature calyces. At 100 nM 4,9-anhydrotetrodotoxin, peak sodium current was reduced on average by 20% in P5–14 calyces, by 37% in mature dimorphic PZ calyces, but by less than 15% in mature CZ calyx-only terminals. In mature PZ calyces, action potentials became shorter and broader in the presence of 4,9-anhydrotetrodotoxin implicating a role for Nav1.6 channels in firing in dimorphic afferents.

Sodium channel diversity in the vestibular ganglion: NaV1.5, NaV1.8, and tetrodotoxin-sensitive currents.

Firing patterns differ between subpopulations of vestibular primary afferent neurons. The role of sodium (NaV) channels in this diversity has not been investigated because NaV currents in rodent vestibular ganglion neurons (VGNs) were reported to be homogeneous, with the voltage dependence and tetrodotoxin (TTX) sensitivity of most neuronal NaV channels. RT-PCR experiments, however, indicated expression of diverse NaV channel subunits in the vestibular ganglion, motivating a closer look. Whole cell recordings from acutely dissociated postnatal VGNs confirmed that nearly all neurons expressed NaV currents that are TTX-sensitive and have activation midpoints between -30 and -40 mV. In addition, however, many VGNs expressed one of two other NaV currents. Some VGNs had a small current with properties consistent with NaV1.5 channels: low TTX sensitivity, sensitivity to divalent cation block, and a relatively negative voltage range, and some VGNs showed NaV1.5-like immunoreactivity. Other VGNs had a current with the properties of NaV1.8 channels: high TTX resistance, slow time course, and a relatively depolarized voltage range. In two NaV1.8 reporter lines, subsets of VGNs were labeled. VGNs with NaV1.8-like TTX-resistant current also differed from other VGNs in the voltage dependence of their TTX-sensitive currents and in the voltage threshold for spiking and action potential shape. Regulated expression of NaV channels in primary afferent neurons is likely to selectively affect firing properties that contribute to the encoding of vestibular stimuli.

Irregular primary otolith afferents from the guinea pig utricular and saccular maculae respond to both bone conducted vibration and to air conducted sound

This study sought to identify in guinea pig the peripheral sense organ of origin of otolith irregular primary vestibular afferent neurons having a very sensitive response to both air-conducted sound (ACS) and bone-conducted vibration (BCV). Neurons responding to both types of stimuli were labelled by juxtacellular labelling by neurobiotin. Whole mounts of the maculae showed that some vestibular afferents activated by both ACS and BCV originate from the utricular macula and some from the saccular macula - there is no "afferent specificity" by one sense organ for ACS and the other for BCV - instead some afferents from both sense organs have sensitive responses to both stimuli. The clinical implication of this result is that differential evaluation of the functional status of the utricular and saccular maculae cannot rely on stimulus type (ACS vs BCV), however the differential motor projections of the utricular and saccular maculae allow for differential evaluation of each sense organ.

Vestibular primary afferent responses to sound and vibration in the guinea pig

This study tested whether air-conducted sound and bone-conducted vibration activated primary vestibular afferent neurons and whether, at low levels, such stimuli are specific to particular vestibular sense organs. In response to 500 Hz bone-conducted vibration or 500 Hz air-conducted sound, primary vestibular afferent neurons in the guinea pig fall into one of two categories--some neurons show no measurable change in firing up to 2 g peak-to-peak or 140 dB SPL. These are semicircular canal neurons (regular or irregular) and regular otolith neurons. In sharp contrast, otolith irregular neurons show high sensitivity: a steep increase in firing as stimulus intensity is increased. These sensitive neurons typically, but not invariably, were activated by both bone-conducted vibration and air-conducted sound, they originate from both the utricular and saccular maculae, and their sensitivity underpins new clinical tests of otolith function.

Resting Discharge Patterns of Macular Primary Afferents in Otoconia-Deficient Mice

Vestibular primary afferents in the normal mammal are spontaneously active. The consensus hypothesis states that such discharge patterns are independent of stimulation and depend instead on excitation by vestibular hair cells due to background release of synaptic neurotransmitter. In the case of otoconial sensory receptors, it is difficult to test the independence of resting discharge from natural tonic stimulation by gravity. We examined this question by studying discharge patterns of single vestibular primary afferent neurons in the absence of gravity stimulation using two mutant strains of mice that lack otoconia (OTO-; head tilt, het-Nox3, and tilted, tlt-Otop1). Our findings demonstrated that macular primary afferent neurons exhibit robust resting discharge activity in OTO- mice. Spike interval coefficient of variation (CV = SD/mean spike interval) values reflected both regular and irregular discharge patterns in OTO- mice, and the range of values for rate-normalized CV was similar to mice and other mammals with intact otoconia although there were proportionately fewer irregular fibers. Mean discharge rates were slightly higher in otoconia-deficient strains even after accounting for proportionately fewer irregular fibers [OTO- = 75.4 +/- 31.1(113) vs OTO+ = 68.1 +/- 28.5(143) in sp/s]. These results confirm the hypothesis that resting activity in macular primary afferents occurs in the absence of ambient stimulation. The robust discharge rates are interesting in that they may reflect the presence of a functionally 'up-regulated' tonic excitatory process in the absence of natural sensory stimulation.

Patient and Normal Three-dimensional Eye-Movement Responses to Maintained (DC) Surface Galvanic Vestibular Stimulation

That disease or dysfunction of vestibular end organs in human patients will reduce or eliminate the contribution of the affected end organs to the total eye-movement response to DC surface galvanic vestibular stimulation (GVS). It was assumed that DC GVS (at current of 5 mA) stimulates all vestibular end organs, an assumption that is strongly supported by physiological evidence, including the activation of primary vestibular afferent neurons by galvanic stimulation. Previous studies also have described the oculomotor responses to vestibular activation. Stimulation of individual semicircular canals results in eye movements parallel to the plane of the stimulated canal, and stimulation of the utricular macula produces changes in ocular torsional position. It was also assumed that the total three-dimensional eye-movement response to GVS is the sum of the contributions of the oculomotor drive of all the vestibular end organs. If a particular vestibular end organ were to be diseased or dysfunctional, it was reasoned that its contribution to the GVS-induced oculomotor response would be reduced or absent and that patients thus affected would have a systematic difference in their GVS-induced oculomotor response compared with the response of normal healthy individuals. Three-dimensional video eye-movement recording was carried out in complete darkness on normal healthy subjects and patients with various types of vestibular dysfunction, as diagnosed by independent vestibular clinical tests. The eye-movement response to long-duration bilateral and unilateral surface GVS was measured. The pattern of horizontal, vertical, and torsional eye velocity and eye position during GVS of patients independently diagnosed with bilateral vestibular dysfunction, unilateral vestibular dysfunction, CHARGE syndrome (semicircular canal hypoplasia), semicircular canal occlusion, or inferior vestibular neuritis differed systematically from the responses of normal healthy subjects in ways that corresponded to the expectations from the conceptual approach of the study. The study reports the first data on the differences between the normal response to GVS and those of patients with a number of clinical vestibular conditions including unilateral vestibular loss, canal block, and vestibular neuritis. The GVS-induced eye-movement patterns of patients with vestibular dysfunction are consistent with the reduction or absence of oculomotor contribution from the end organs implicated in their particular disease condition.

Molecular characterization of two novel splice variants of G alphai2 in the rat vestibular periphery

GTP binding proteins play an important role in mediating signals transduced across the cell membrane by membrane-bound receptors. We previously described a partial sequence, termed Galphai2vest, obtained from rat vestibular tissue that was nearly identical to rat Galphai2. Using an experimental strategy to further characterize Galphai2vest (GenBank accession number AF189020) and identify other possible Galphai2-related transcripts expressed in the rat vestibular periphery, we employed a RecA-based gene enrichment protocol in place of conventional library screening techniques. We identified two novel Galphai2 splice variants, Galphai2(a) (GenBank accession number AY899210) and Galphai2(b) (GenBank accession number AY899211), that have most of exons 8 and 9 deleted, and exons 5 through 9 deleted, respectively. In situ hybridization studies were completed to determine the differential expression of Galphai2 between the vestibular primary afferent neurons and the vestibular end organs. Computer modeling and predicted 3D conformation of the wild type Galphai2 and the two splice variants were completed to evaluate the changes associated with the Gbetagamma and GTP binding sites. These two novel alternatively spliced isoforms of Galphai2 putatively encode truncated proteins that could serve unique roles in the physiology of the vestibular neuroepithelium. Galphai2vest was found to be a processed pseudogene.

前庭神経系の化学的神経機能解剖

Vestibular neurons in the internal auditory canal are composed of afferent and efferent fibers. Vestibular primary afferent neurons have their cell somata, so-called Scarpa's ganglion cells, localized in the canal. Vestibular afferents receive afferent signals from vestibular hair cells and transmit them to vestibular nuclei and vestibulocerebellum. Vestibular afferents also receive efferent signals via axo-dendritic synapses between calyxes and vestibular efferent fibers. According to the afferent and efferent information, vestibular afferents have crucial bipolar effects both on distal and proximal synapses. In this review article, I would like to discuss the roles of vestibular neurons, including both afferents and efferents, in terms of neurotransmitters and neuromodulators.

Dynamics and the single spike.

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

Differential impact of hypergravity on maturating innervation in vestibular epithelia during rat development

Over the past decades, the new opportunity of space flights has revealed the importance of gravity as a mechanical constraint for terrestrial organisms as well as its influence on the somatosensory system. The lack of gravitational reference in orbital flight induces changes in equilibrium, with major modifications involving neuromorphological and physiological adaptations. However, few data have illustrated the putative effect of gravity on sensory vestibular epithelial development. We asked if gravity, the primary stimulus of utricles could act as an epigenetic factor. As sensorial deprivation linked to weightlessness is technically difficult, we used a ground-based centrifuge to increase the gravitational vector, in order to hyperstimulate the vestibule. In this study, 3 days after mating, pregnant females were submitted to hypergravity, 2 g (HG). Their embryos were raised, born and postnatally developed under HG. The establishment of connections between primary vestibular afferent neurons and hair cells in the utricle of these young rats was followed from birth to postnatal day 6 (PN6) and compared to embryos developed in normogravity (NG): Immunocytochemistry for neurofilaments and microvesicles revealed the differential effects of gravity on the late neuritogenic and synaptogenic processes in utricles. Taking type I hair cell innervation as a criterion of maturation, we found that primary afferent fibres reached the vestibular epithelium and enveloped hair cells in the same way, both under NG and HG. Thus, this phenomenon of leading growth cones to their epithelial target appears to be dependent on intrinsic genetic properties and not on an external stimulus. In contrast, the maturation of connection processes between type 1 hair cells and the afferent calyx, concerning specifically the microvesicles at their apex, was delayed under HG. Therefore, gravity appears to be an epigenetic factor influencing the late maturation of utricles. These differential effects of altered gravity on the development of the vestibular epithelium are discussed.

Peripheral patterns of terminal innervation of vestibular primary afferent neurons projecting to the vestibulocerebellum in the gerbil.

Retrograde transganglionic labeling techniques with biotinylated dextran amine (BDA) were used to examine the terminal field structure and topographical patterns of innervation within the vestibular sensory end organs of vestibular primary afferent neurons projecting to the cerebellar uvula/nodulus and flocculus lobules in the gerbil. Robust, dark labeling in the cristae ampullares suggested that the vast majority of the terminals of afferent neurons were of the dimorphic type. The majority (94% to the uvula/nodulus and 100% to the flocculus) innervates the peripheral zones of each of the three semicircular canal cristae. Comparison of the type and distribution of terminals across the canalicular sensory neuroepithelium with morphophysiological studies in chinchilla suggests that the labeled population consists predominantly of peripheral terminal fields of lower-to-intermediate gain, more regularly firing, tonic afferents. For otolith organ-related afferents, the uvula/nodulus receives strong inputs from primary otolith afferent neurons identified as dimorphic in type that predominately innervate the peristriolar zones of the utricular and saccular maculae. No direct otolith organ-related inputs to the flocculus were observed. In contrast to the canal afferents, the types and locations of labeled otolith afferent terminals suggest that they largely consist of irregularly firing, high-gain, phasic neurons.

Evidence for three additional P2X 2 purinoceptor isoforms produced by alternative splicing in the adult rat vestibular end-organs

P2X 2 receptors are ligand-gated ion channels that are activated by extracellular ATP. To characterize the expression of P2X 2 purinoceptor in the adult rat vestibular periphery, reverse transcription-polymerase chain reaction (RT-PCR) was used. No transcript for P2X 2 receptor was found in the vestibular primary afferent neurons (Scarpa's ganglia); however, partial cDNAs encoding four splice variants of the P2X 2 receptor were isolated from vestibular end-organs. In all four cDNAs, the deletions were of different lengths but started at the same position on the P2X 2 gene (Val-370 codon) located toward the intracellular carboxyl terminus. One of these receptor isoforms was identical in sequence to the recently published P2X 2(b) receptor (Simon et al., 1997, Mol. Pharmacol. 52, 237–248) (also known as P2X 2-2, in the nomenclature of Brändle et al., 1997, FEBS Lett. 404, 294–298). The remaining three novel splice variants of the P2X 2 receptor were designated P2X 2(e), P2X 2(f) and P2X 2(g) (GenBank accession numbers AF028603, AF028604 and AF028605, respectively). The functional significance of these three splice variants remains to be determined. Pituitary and cerebellum were used as survey tissues and only the P2X 2(b) receptor cDNA was found.

Extracellular nucleotide signaling in the inner ear.

Extracellular nucleotides, particularly adenosine 5'-triphosphate (ATP), act as signaling molecules in the inner ear. Roles as neurotransmitters, neuromodulators, and as autocrine or paracrine humoral factors are evident. The diversity of the signaling pathways for nucleotides, which include a variety of ATP-gated ion channels (assembled from different subtypes of P2X-receptor subunit) and also different subtypes of G protein-coupled nucleotide receptors (P2Y receptors) supports a major physiological role for ATP in the regulation of hearing and balance. Almost invariably both P2X and P2Y receptor expression is apparent in the complex tissue structures associated with the inner-ear labyrinth. However P2X-receptor expression, commonly associated with fast neurotransmission, is apparent not only with the cochlear and vestibular primary afferent neurons, but also appears to mediate humoral signaling via ATP-gated ion channel localization to the endolymphatic surface of the cochlear sensory epithelium (organ of Corti). This is the site of the sound-transduction process and recent data, including both electrophysiological, imaging, and immunocytochemistry, has shown that the ATP-gated ion channels are colocalized here with the mechano-electrical transduction channels of the cochlear hair cells. In contrast to this direct action of extracellular ATP on the sound-transduction process, an indirect effect is apparent via P2Y-receptor expression, prevalent on the marginal cells of the stria vascularis, a tissue that generates the standing ionic and electrical gradients across the cochlear partition. The site of generation of these gradients, including the dark-cell epithelium of the vestibular labyrinth, may be under autocrine or paracrine regulation mediated by P2Y receptors sensitive to both purines (ATP) and pyrimidines such as UTP. There is also emerging evidence that the nucleoside adenosine, formed as a breakdown product of ATP by the action of ectonucleotidases and acting via P1 receptors, is also physiologically significant in the inner ear. P1-receptor expression (including A1, A2, and A3 subtypes) appear to have roles associated with stress, acting alongside P2Y receptors to enhance cochlear blood flow and to protect against the action of free radicals and to modulate the activity of membrane conductances. Given the positioning of a diverse range of purinergic-signaling pathways within the inner ear, elevations of nucleotides and nucleosides are clearly positioned to affect hearing and balance. Recent data clearly supports endogenous ATP- and adenosine-mediated changes in sensory transduction via a regulation of the electrochemical gradients in the cochlea, alterations in the active and passive mechanical properties of the cells of the sensory epithelium, effects on primary afferent neurons, and control of the blood supply. The field now awaits conclusive evidence linking a physiologically-induced modulation of extracellular nucleotide and nucleoside levels to altered inner ear function.

Differential expression of α2–7, α9 and β2–4 nicotinic acetylcholine receptor subunit mRNA in the vestibular end-organs and Scarpa's ganglia of the rat

To further characterize the pattern of expression of the nicotinic acetylcholine receptor (nAChR) subunits in the peripheral vestibular system, we conducted RT-PCR of all known mammalian nAChR α and β subunits in mRNA extracted from adult rat vestibular primary afferent neurons (Scarpa's ganglia) and vestibular end-organs. Transcripts encoding the α2–7 and β2–4 nAChR subunits were found in the vestibular ganglia, while α3, α5–7, α9 and β2–4 nAChR subunits were expressed in the vestibular end-organs. These results support previous electrophysiological, immunocytochemical and molecular biological data, and also provide a more complete understanding of the role of nAChRs in the neurochemical transmission subserving the efferent–afferent interaction in the vestibular periphery.

前庭神経節細胞のシトクロム酸化酵素活性

Cyochrome oxidase (CO) activity of primary vestibular afferent neurons in Scarpa's ganglion of the squirrel monkey was demonstrated histochemically under normal and experimental conditions. The right vestibular nerve of adult squirrel monkeys was sectioned between Scarpa's ganglion and the brainstem under general anesthesia. The left side was used as a normal control. Following a survival period of seven months, neurons in Scarpa's ganglion on both sides were examined. In normal sides, a negative correlation was observed between the sizes of the neurons and their CO activities. The vestibular neurons in the transected side survived, but their cell sizes and CO activities were reduced in comparison with those on the control side.

Immunocytochemical Localization of Substance P and Neurofilament Proteins in the Guinea Pig Vestibular Ganglion

To examine the cytochemical features of primary vestibular afferent neurons, we examined the immunocytochemical distribution of substance P(SP) and neurofilament proteins (NFP) in the guinea pig vestibular endorgans and ganglion. 84.9% of vestibular ganglion cells showed SP-like immunoreactivity. SP immunoreactive cells were small in diameter (25.4 microns), and randomly distributed in the ganglia. NFP immunoreactive cells (34.2%) were relatively large in diameter (31.1 microns). By double-staining immunocytochemistry it was possible to distinguish three different cell types: SP-positive/NFP-negative, SP-negative/NFP-positive, and SP/NFP-positive vestibular ganglion cells. Vestibular ganglion cells can thus be classified on the basis of size and immunocytochemical characteristics. These chemically distinct subpopulations of vestibular ganglion cells may be an indication of functional differences within vestibular afferent neurons.

The electrically evoked vestibulo‐ocular reflex: I. normal subjects

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

Voluntary control of the human vestibulo-ocular reflex.

The ability of normal subjects to increase their vestibulo-ocular reflex (VOR) gain with an imagined stationary frame of reference was dependent on their strategy and the test conditions. With large amplitude sinusoidal rotation (greater than 50 degrees) subjects could not increase their VOR gain regardless of the strategy used. With small amplitude excursions (less than 50 degrees) they could significantly increase their VOR gain if they used a 'single stripe' strategy. Accompanying this increase in VOR gain was an increase in the phase lead of VOR slow phase velocity relative to head velocity. Apparently the signal used to augment the VOR gain with an imagined stationary surround had phase characteristics similar to those of primary vestibular afferent neurons.