Sound Coding in the Auditory Nerve: From Single Fiber Activity to Cochlear Mass Potentials in Gerbils.

Auditory nerve fibers (ANFs) convey acoustic information from the sensory cells to the brainstem using an elaborated neural code based on both spike timing and rate. As the stimulus tone frequency increases, time coding fades and ceases, resulting in high-frequency tone encoding that relies mostly on the spike discharge rate. Here, we recapitulated our recent single-unit data from gerbil's auditory nerve to highlight the most relevant mode of coding (spike timing versus spike rate) in tone-in-noise. We report that high-spontaneous rate (SR) fibers driven by low-frequency tones in noise are able to phase lock ∼30 dB below the level that evoked a significant elevation of the discharge rate, whereas medium- and low-SR fibers switch their preferential mode of coding from rate coding in quiet, to time coding in noise. For high-frequency tone, the low-threshold/high-SR fibers reach their maximum discharge rate in noise and do not respond to tones, whereas medium- and low-SR fibers are still able to respond to tones making them more resistant to background noise. Based on these findings, we first discuss the ecological function of the ANF distribution according to their spontaneous discharge rate. Then, we point out the poor synchronization of the low-SR ANFs, accounting for the discrepancy between ANF number and the amplitude of the compound action potential of the of the auditory nerve. Finally, we proposed a new diagnostic tool to assess low-SR fibers, which does not rely on the onset response of the ANFs.

Histamine H4 receptor antagonists as potent modulators of mammalian vestibular primary neuron excitability.

BACKGROUND AND PURPOSE: Betahistine, the main histamine drug prescribed to treat vestibular disorders, is a histamine H(3) receptor antagonist. Here, we explored the potential for modulation of the most recently cloned histamine receptor (H(4) receptor) to influence vestibular system function, using a selective H(4) receptor antagonist JNJ 7777120 and the derivate compound JNJ 10191584. EXPERIMENTAL APPROACH: RT-PCR was used to assess the presence of H(4) receptors in rat primary vestibular neurons. In vitro electrophysiological recordings and in vivo behavioural approaches using specific antagonists were employed to examine the effect of H(4) receptor modulation in the rat vestibular system. KEY RESULTS: The transcripts of H(4) and H(3) receptors were present in rat vestibular ganglia. Application of betahistine inhibited the evoked action potential firing starting at micromolar range, accompanied by subsequent strong neuronal depolarization at higher concentrations. Conversely, reversible inhibitory effects elicited by JNJ 10191584 and JNJ 7777120 began in the nanomolar range, without inducing neuronal depolarization. This effect was reversed by application of the selective H(4) receptor agonist 4-methylhistamine. Thioperamide, a H(3) /H(4) receptor antagonist, exerted effects similar to those of H(3) and H(4) receptor antagonists, namely inhibition of firing at nanomolar range and membrane depolarization above 100 µM. H(4) receptor antagonists significantly alleviated the vestibular deficits induced in rats, while neither betahistine nor thioperamide had significant effects. CONCLUSIONS AND IMPLICATIONS: H(4) receptor antagonists have a pronounced inhibitory effect on vestibular neuron activity. This result highlights the potential role of H(4) receptors as pharmacological targets for the treatment of vestibular disorders.

TRPV4 channels mediate the infrared laser-evoked response in sensory neurons.

Infrared laser irradiation has been established as an appropriate stimulus for primary sensory neurons under conditions where sensory receptor cells are impaired or lost. Yet, development of clinical applications has been impeded by lack of information about the molecular mechanisms underlying the laser-induced neural response. Here, we directly address this question through pharmacological characterization of the biological response evoked by midinfrared irradiation of isolated retinal and vestibular ganglion cells from rodents. Whole cell patch-clamp recordings reveal that both voltage-gated calcium and sodium channels contribute to the laser-evoked neuronal voltage variations (LEVV). In addition, selective blockade of the LEVV by micromolar concentrations of ruthenium red and RN 1734 identifies thermosensitive transient receptor potential vanilloid channels as the primary effectors of the chain reaction triggered by midinfrared laser irradiation. These results have the potential to facilitate greatly the design of future prosthetic devices aimed at restoring neurosensory capacities in disabled patients.

Comparison of the pharmacological properties of GK11 and MK801, two NMDA receptor antagonists: towards an explanation for the lack of intrinsic neurotoxicity of GK11.

Over-stimulation of NMDA receptors (NMDARs) is involved in many neurodegenerative disorders. Thus, developing safe NMDAR antagonists is of high therapeutic interest. GK11 is a high affinity uncompetitive NMDAR antagonist with low intrinsic neurotoxicity, shown to be promising for treating CNS trauma. In the present study, we investigated the molecular basis of its interaction with NMDARs and compared this with the reference molecule MK801. We show, on primary cultures of hippocampal neurons, that GK11 exhibits neuroprotection properties similar to those of MK801, but in contrast with MK801, GK11 is not toxic to neurons. Using patch-clamp techniques, we also show that on NR1a/NR2B receptors, GK11 totally blocks the NMDA-mediated currents but has a six-fold lower IC(50) than MK801. On NR1a/NR2A receptors, it displays similar affinity but fails to totally prevent the currents. As NR2A is preferentially localized at synapses and NR2B at extrasynaptic sites, we investigated, using calcium imaging and patch-clamp approaches, the effects of GK11 on either synaptic or extrasynaptic NMDA-mediated responses. Here we demonstrate that in contrast with MK801, GK11 better preserve the synaptic NMDA-mediated currents. Our study supports that the selectivity of GK11 for NR2B containing receptors accounts contributes, at least partially, for its safer pharmacological profile.

Hyperpolarization-activated (Ih) current in mouse vestibular primary neurons.

The presence of a hyperpolarization-activated inward current (Ih) was investigated in mouse vestibular primary neurons using the whole-cell patch-clamp technique. In current-clamp configuration, injection of hyperpolarizing currents induced variations of membrane voltage with prominent time-dependent rectification increasing with current amplitudes. This effect was abolished by 2 mM Cs+ or 100 microM ZD7288. In voltage-clamp configuration, hyperpolarization pulses from -60 mV to -140 mV triggered a slow activating and non inactivating inward current that was sensitive to the two blockers, but insensitive to 5 mM Ba2+. Changing Na+ and K+ concentrations demonstrated that Ih current is carried by both these monovalent cations. This is the first demonstration of a Ih current in vestibular primary neurons.

Three types of depolarization-activated potassium currents in acutely isolated mouse vestibular neurons.

The nature and electrophysiological properties of Ca(2+)-independent depolarization-activated potassium currents were investigated in vestibular primary neurons acutely isolated from postnatal mice using the whole cell configuration of the patch-clamp technique. Three types of currents were identified. The first current, sensitive to TEA (I(TEA)) and insensitive to 4-aminopyridine (4-AP), activated at -40 mV and exhibited slow activation (tau(ac), 38.4 +/- 7.8 ms at -30 mV, mean +/- SD). I(TEA) had a half activation potential [V(ac(1/2))] of -14.5 +/- 2.6 mV and was inactivated by up to 84.5 +/- 5.7% by 10-s conditioning prepulses with a half inactivation potential [V(inac(1/2))] of -62.4 +/- 0.2 mV. The second current, sensitive to 4-AP (maximum block around 0.5 mM) and to alpha-dendrotoxin (I(DTX)) appeared at -60 mV. Complete block of I(DTX) was achieved using either 20 nM alpha-DTX or 50 nM margatoxin. This current activated 10 times faster than I(TEA) (tau(ac), 3.5 +/- 0.8 ms at -50 mV) with V(ac(1/2)) of -51.2 +/- 0.6 mV, and inactivated only slightly compared with I(TEA) (maximum inactivation, 19.7 +/- 3.2%). The third current, also sensitive to 4-AP (maximum block at 2 mM), was selectively blocked by application of blood depressing substance (BDS-I; maximum block at 250 nM). The BDS-I-sensitive current (I(BDS-I)) activated around -60 mV. It displayed fast activation (tau(ac), 2.3 +/- 0.4 ms at -50 mV) and fast and complete voltage-dependent inactivation. I(BDS-I) had a V(ac(1/2)) of -31.3 +/- 0.4 mV and V(inac(1/2)) of -65.8 +/- 0.3 mV. It displayed faster time-dependent inactivation and recovery from inactivation than I(TEA). The three types of current were found in all the neurons investigated. Although I(TEA) was the major current, the proportion of I(DTX) and I(BDS-I) varied considerably between neurons. The ratio of the density of I(BDS-I) to that of I(DTX) ranged from 0.02 to 2.90 without correlation with the cell capacitances. In conclusion, vestibular primary neurons differ by the proportion rather than the type of the depolarization-activated potassium currents they express.

Efferent function of vestibular afferent endings? Similar localization of N-type calcium channels, synaptic vesicle and synaptic membrane-associated proteins.

We investigated the distribution of N-type voltage-dependent calcium channels that mediate Ca(2+) entry initiating transmitter release in the rat vestibular sensory epithelium. We used confocal microscopy to assess the in vitro labeling by fluorescent specific ligand binding, omega-conotoxin-GVIA and also the immunolabeling of presynaptic soluble N-ethylmaleimide-sensitive fusion factor attachment protein receptor (SNARE) proteins, syntaxin, 25,000 mol. wt synaptosome-associated protein and synaptotagmin: components of the neurotransmitter exocytosis machinery. We found that there was a close anatomical association between the voltage-gated calcium channels, the synaptic vesicle and synaptic membrane-associated proteins on the afferent nerve calyces and probably afferent boutons, which are postsynaptic compartments. Our data suggest that these peripheral afferent endings possess the presynaptic Ca(2+) channels and the components of the presynaptic SNARE proteins involved in synaptic vesicle docking and calcium-dependent exocytosis. They provide additional evidence for a secretory function and efferent role of these endings in hair cell neurotransmission.

Developmental changes in low and high voltage-activated calcium currents in acutely isolated mouse vestibular neurons.

1. The development of low voltage-activated (LVA) and high voltage-activated (HVA) calcium currents was studied in neurons acutely dissociated from mouse vestibular ganglia at embryonic stages (E)14, 15, 17 and birth using the whole-cell patch-clamp technique. 2. LVA current was present in almost all neurons tested at stages E14 to E17, although at birth this current was restricted to a few neurons. Two populations of neurons were characterized based on the amplitude of the LVA current. In the first population, LVA current densities decreased between E17 and birth by which time this current tended to disappear in most neurons. A second population of neurons with high density LVA current appeared at E17, and in this group the mean density increased during development. 3. Among HVA currents, the dihydropyridine-sensitive L-type current remained constant between E15 and birth. Over the same period, the density of N- and Q-type currents continuously increased as shown using omega-conotoxin-GVIA (N-type), and high concentrations of omega-agatoxin-IVA (Q-type). The P-type current, sensitive to low concentrations of omega-agatoxin-IVA, transiently increased between E15 and E17, and then both current density and its proportion of the global current decreased. 4. Our results reveal large modifications in the expression of voltage-dependent calcium channels during embryonic development of primary vestibular neurons. The changes in the expression of LVA current and the transient augmentation of P-type HVA current occur during a period characterized by massive neuronal growth and by the beginning of synaptogenesis. These results suggest a specific role of these currents in the ontogenesis of vestibular primary afferents.

Developmental regulation of T-, N- and L-type calcium currents in mouse embryonic sensory neurones.

We investigated the development of a low (T-type) and two high voltage-activated (N- and L-type) calcium channel currents in large diameter dorsal root ganglion neurones acutely isolated from embryonic mice using the whole-cell patch-clamp technique. The low and high voltage-activated barium currents (LVA and HVA) were identified by their distinct threshold of activation and their sensitivity to pharmacological agents, dihydropyridines and omega-conotoxin-GVIA, at embryonic day 13 (E13), E15 and E17-18, respectively, before, during and after synaptogenesis. The amplitude and density of LVA currents, measured during a -40 mV pulse from a holding potential of -100 mV, increased significantly between E13 and E15, and remained constant between E15 and E17-18. The density of global HVA current, elicited by 0 mV pulse, increased between E13 and E15/E17-18. The density of the N-type current studied by the application of omega-conotoxin-GVIA (1 microM) increased significantly between E13 and E15/E17-18. The use of the dihydropyridine nitrendipine (1 microM) revealed that the density of L-type current remained constant at each stage of development. Nevertheless, application of dihydropyridine Bay K 8644 (3 microM) demonstrated a significant slowing of the deactivation tail current between embryonic days 13 and 15, which may reflect a qualitative maturation of this class of calcium channel current. The temporal relationship between the changes in calcium channel pattern and the period of target innervation suggests possible roles of T-, N- and L-type currents during developmental key events such as natural neurone death and onset of synapse formation.

Toxin-resistant calcium currents in embryonic mouse sensory neurons.

We characterized toxin-insensitive calcium currents expressed by acutely dissociated embryonic dorsal root ganglion neurons. In the presence of 3 microM omega-conotoxin-GVIA, 3 microM nitrendipine and either 500 nM omega-agatoxin-IVA or 500 nM omega-conotoxin-MVIIC to inhibit N-, L- and P/Q-type currents, respectively, all neurons expressed two residual currents: a T-type and another which we referred to as toxin-resistant current. The toxin-resistant current (i) consisted of an inactivating and a sustained components, (ii) had a threshold of activation and a steady-state inactivation comprised between that of the T-type current and that of the other high-voltage-activated currents, (iii) had the same permeability for barium and calcium used as charge carriers, (iv) was highly sensitive to both cadmium and nickel; and (v) was insensitive to 500 microM amiloride which abolished the T-type at this concentration. The properties of the toxin-resistant current are very similar to those of the currents expressed in oocytes following injection of alpha(1E) subunits which we demonstrated to be present in these neurons. Therefore a component of the toxin-resistant current calcium channels in sensory neurons may be closely related to those calcium channels formed by alpha(1E) subunits.

Multiple voltage-dependent calcium currents in acutely isolated mouse vestibular neurons.

We investigated the presence of voltage-gated calcium currents in vestibular neurons acutely isolated from postnatal mice vestibular ganglions using the whole-cell patch-clamp technique. The neuronal origin of the recorded cells was confirmed by immunohistochemical detection of neurofilaments and calretinin. High and low voltage-activated calcium currents were recorded. High voltage-activated currents were present in all investigated neurons. Low voltage-activated currents were recorded in only a few large vestibular neurons. High and low voltage-activated currents were distinguished by their thresholds of activation and their ability to run-up during early recordings. Among high voltage-activated currents. L-, N- and P-type currents were identified by their sensitivity to, respectively, the dihydropyridines agonist Bay K 8644 (3 microM) and antagonist nitrendipine (3 microM), the co-conotoxin GVIA (3 microM) and the omega-agatoxin IVA at low concentration (50 nM). An inactivating current sensitive to 1 microM omega-agatoxin IVA with characteristics similar to those of the Q-type current was also recorded in vestibular neurons. When L-, N-, P-, Q-type barium currents were blocked, a residual high voltage-activated current defined by its resistance to saturating concentrations of all above blockers was detected. This residual current was completely blocked by 0.5 mM nickel and cadmium. Our results reveal that primary vestibular neurons express a variety of voltage-activated calcium currents with distinct physiological and pharmacological properties. This diversity could be related both with their functional synaptic characteristic, and with the intrinsic physiological properties of each class of vestibular afferents.

Voltage-activated sodium currents in acutely isolated mouse vestibular ganglion neurones.

Voltage-activated sodium currents (INa) in vestibular ganglion neurones acutely isolated from postnatal mice were investigated using the whole-cell configuration of the patch-clamp technique. Under recording conditions designed to allow the complete isolation of INa depolarizations from a holding potential of -80 mV revealed a fast inactivating inward current which was activated around -60 mV and exhibited maximum peak current around -30 mV. This current was eliminated when the cells were perifused with a Na(+)-free solution and almost totally blocked by application of 100 nM tetrodotoxin (TTX). These properties identify this inward current as TTX-sensitive INa. The half-maximum activation potential of INa was -46 mV and its half-maximum inactivation potential was -69 mV. This is the first report of voltage-activated sodium currents in vestibular primary neurones.

Opposite developmental regulation of P- and Q-type calcium currents during ontogenesis of large diameter mouse sensory neurons.

Analysis of neuronal development has emphasized the importance of voltage-activated Ca2+ currents during the initial period of differentiation. We investigated non-N, non-L Ba2+ currents through Ca2+ channels in freshly dissociated large diameter embryonic mouse dorsal root ganglion neurons using the whole-cell patch-clamp technique. Two types of omega-agatoxin IVA-sensitive currents were clearly distinguished at embryonic day 13: a sustained P-type current blocked selectively at 30 nM (IC50 = 3nM) and an inactivating Q-type current blocked in the range 50-500 nM (IC50 = 120nM). The P-type Ca2+ current disappeared at day 15 whereas the Q-type Ca2+ current increased two- to three-fold during the same embryonic period. In contrast, the contribution of the non-L, non-N, omega-agatoxin IVA-resistant current (R-type) was constant during this developmental span. In conclusion, our results clearly show that P- and Q-type Ca2+ currents are differentially expressed during ontogenesis in large diameter dorsal root ganglion neurons. The developmental change, which occurs during the period of target innervation, could be related to specific key events such as natural neuron death and onset of synapse formation.

Neurofilament proteins form an annular superstructure in guinea-pig type I vestibular hair cells.

Neurofilaments, the neuron-specific intermediate filaments, are composed of three immunochemically distinct subunits: NF-L, NF-M and NF-H that can be either phosphorylated or unphosphorylated. In mammals, the distribution of these subunits has been described in vestibular ganglion neurons, but there are no reports on the presence of neurofilaments in vestibular hair cells. We investigated, by immunocytochemistry, neurofilaments in vestibular hair cells from rat and guinea-pig using antibodies against the three subunits and to dephosphorylated NF-H (clone SMI 32, recognizes also NF-M on immunoblots), on Vibratome sections of the vestibular end-organs and on isolated hair cells. Various immunostaining protocols were used, as appropriate for the method of observation: laser scanning confocal microscopy (immunofluorescence) and transmission electron microscopy (immunoperoxidase, pre-embedding technique). In rat and guinea-pig cristae and utricles, neurofilament immunoreactivity was observed in axons inside and below the sensory epithelia. In guinea-pig, in addition to this staining, intensely immunoreactive annular structures were found in the basal regions of hair cells. These rings were detected with anti-NF-L, -NF-M and -dephosphorylated NF-H/M antibodies, but not with anti-phosphorylation-independent NF-H. Ring-containing hair cells were present in all regions of the sensory epithelia but were more abundant in the peripheral areas. All levels of observation (Vibratome and thin sections, and isolated hair cells) showed that only the guinea-pig type I hair cells contained a neurofilament ring. High-resolution observations showed that the ring was located below the nucleus, often close to smooth endoplasmic reticulum and the cell membrane.

Development of calretinin immunoreactivity in the mouse inner ear.

Calretinin is a calcium-binding protein of the EF-hand family. It has been previously identified in particular cell types of adult guinea pig, rat, and chinchilla inner ear. Development of calretinin immunoreactivity in the mouse inner ear was investigated from embryonic day 13 (E13) to the adult stage. In the adult mouse vestibule, calretinin immunoreactivity was present in the same structures as described for the rat and guinea pig: the population of afferent fibers forming calyx units and a small number of ganglion neurons. The earliest immunoreactivity was found at E17 in vestibular hair cells (VHCs), then, at E19, in afferent fibers entering the sensory epithelia and in rare ganglion neurons. At postnatal day 4 (P4), a few vestibular nerve fibers and ganglion neurons were reactive. From this stage until P14, immunoreactivity developed in the calyx units and disappeared from VHCs. At P14, immunostaining was adult-like. In the adult mouse cochlea, immunoreactivity was present in the same cell populations as described in the rat: the inner hair cells (IHCs) and most of Corti's ganglion neurons. Calretinin immunoreactivity appeared at E19-P0 in IHCs and ganglion neurons of the basal turn. At P1, outer hair cells (OHCs) of the basal turn were positive. Calretinin immunoreactivity then appeared in IHCs, OHCs, and ganglion neurons of the medial turn, then of the apical turn. At P4, all IHCs and OHCs and most of the ganglion neurons were immunostained. Immunoreactivity gradually disappeared from the OHCs starting at P10 and, at P22, only IHCs and ganglion neurons were positive. The sequences of appearance of calretinin were specific to each cell type of the inner ear and paralleled their respective maturation. Calretinin was transiently expressed in VHCs and OHCs.

Different calcium-binding proteins identify subpopulations of vestibular ganglion neurons in the rat.

Vestibular neurons were studied by cytochrome oxidase (CO) histochemistry and by immunocytochemistry using antibodies against parvalbumin (PV), calbindin (CaBP), calretinin (CaR) and 160 KD neurofilament protein (NF). All the neurons present a high level of CO activity and a high content of PV. CaBP and CaR are restricted to a specific population of about 16% of the neurons and are among the largest ones. The latter neurons also have a high density of NF 160 KD protein. In conclusion the biochemical characteristics of the vestibular ganglion neurons are discussed in relation to their morphological and physiological properties.

[Vestibular evoked potentials. Diagnostic trends]. / Potentiels évoqués vestibulaires. Perspectives diagnostiques.

The contribution of short-latency evoked potentials to the exploration of auditory, visual and somatosensory neurosensory pathways is capital. The determination of short-latency vestibular evoked potentials has encountered many difficulties, mainly due to the necessity to find a specific, very short stimulation in order to select and synchronize the vestibular nerve fibers. Recent studies in animals have demonstrated short-latency potentials evoked by angular accelerations, linear accelerations or electric shocks on the round window. The generators of these potentials seem to be located in the vestibular nerve and nuclei. Electric stimulations of the internal ear have the advantage of providing a study of the peripheral vestibular pathways separately on both sides, while accelerations involve both vestibula, which probably makes the interpretation of data very difficult.

Calretinin immunoreactivity in chinchilla and guinea pig vestibular end organs characterizes the calyx unit subpopulation.

Immunohistochemical investigations with calretinin, a neuronal calcium binding protein, were made in the vestibular end organs of five guinea pigs and one chinchilla. A specific pattern of immunoreactivity of afferent nerve fibers was found. Immunostaining was restricted to thick fibers innervating the apex of the cristae or the striola of the utricular macula. A study of serial sections revealed that the stained afferents gave rise to calyx endings, but not to collaterals containing bouton endings. The results are consistent with the conclusion that, of the three classes of fibers defined by Fernández et al. (1988, 1990), only calyx units are calretinin immunoreactive. A count of the number of labelled fibers in the chinchilla crista suggests that the entire population of calyx units is immunoreactive. The conclusion is surprising since the physiology of calyx units does not differ qualitatively from that of other afferents (Baird et al. 1988; Goldberg et al. 1990). The presence of this protein in the calyx neurons may be related to specific post-synaptic functions of this type of afferents.

Postnatal developmental changes in the responses of mouse primary vestibular neurons to externally applied galvanic currents.

The ontogenesis of vestibular primary neuron sensitivity to depolarisation produced by galvanic current stimulations was studied in mouse inner ear explants maintained in vitro. Cathodal galvanic stimulations, which elicit an increase of the discharge frequencies, are assumed to act on the spike initiation site by depolarizing the neuron. The responses of neurons to galvanic currents at various developmental stages were recorded. The pattern of responses reflected the sensitivities of the neurons to depolarization. At birth, about 75% of the vestibular neurons responded weakly to high intensity galvanic currents thus indicating that they were able to generate action potentials. However, the very low gain of the response to the stimulation revealed the immaturity of the neurons at the spike generation site. Between the day of birth and the ninth postnatal day, an increase in the gain of the responses was observed, indicating the enhancement of the sensitivity of the vestibular neurons to the galvanic currents. This increase in sensitivity was more pronounced from the fourth postnatal day. The response of the neurons to galvanic stimulation increased gradually during postnatal development without reaching a plateau at postnatal day 9 indicating that a further physiological maturation occurs after this stage. These results are consistent with the morphological maturation of the vestibular primary afferents and with previous studies showing that the physiological maturation parallels myelination of the afferent fibers.

The vestibular nerve of the chinchilla. IV. Discharge properties of utricular afferents.

1. Extracellular recording techniques were used in the chinchilla to study the discharge properties of utricular afferents, including their discharge regularity, background discharge, and responses to both externally applied galvanic currents and centrifugal forces. 2. A normalized coefficient of variation (CV*), independent of discharge rate, was used to classify units as regularly (CV* less than 0.10), intermediate (0.10 less than or equal to CV* less than or equal to 0.20), or irregularly discharging (CV* greater than 0.20). In some circumstances, it was useful to recognize a group of very regularly discharging afferents (CV* less than 0.05). The CV* ranged from less than 0.020 to greater than 0.60. Regular units outnumbered irregular units by an approximate 3:1 ratio. The distribution of CV*s was bimodal: there was a major peak at CV* = 0.03 and a minor peak at CV* = 0.3. 3. Background rates were measured with the head in a horizontal position. Those of regular units usually fell between 40 and 80 spikes/s (mean: 54 spikes/s); those of irregular units were more broadly distributed (mean: 47 spikes/s). 4. Units were categorized in terms of the tilt directions resulting in increased discharge. There is a broad distribution of excitatory tilt directions with some units excited by ipsilateral rolls, others by contralateral rolls, some by nose-up pitches, and still others by nose-down pitches. In the chinchilla, there are almost equal numbers of units excited by ipsilateral or contralateral tilts. This is in contrast to previous findings in the cat and squirrel monkey, where the former units predominant by a 3:1 ratio. The difference can be related to the fact that the medial zone of the macula, where units excited by ipsilateral tilts reside, makes up a smaller proportion of the sensory epithelium in the chinchilla than in the monkey. 5. Galvanic sensitivity (beta *) and discharge regularity (CV*) were related by a power law, beta* = (CV*), with an exponent, b = 0.70. 6. Responses to sinusoidal centrifugal forces in the frequency range, f, between DC and 2 Hz were characterized by their gains (gf) and phases (phi f), taken with respect to peak linear force. Response linearity was studied by varying the amplitude of a 0.1-Hz sinusoid from 0.05 to 0.4 g. Nonlinear distortion was small (approximately 10%), as was the variation of gain (+/- 10%) and phase (+/- 5 degrees) with amplitude. 7. Response dynamics vary with discharge regularity. Very regular units are tonic. Their gains are typically 50 spikes.s-1/g and almost constant (+/- 10%) over the entire frequency range. Phases hover near zero with small (5 degrees) phase leads at low frequencies and slightly larger (10 degrees) phase lags at high frequencies. Irregular units are more phasic.(ABSTRACT TRUNCATED AT 400 WORDS)