Gentamicin is toxic to vestibular hair cells, but its effects on vestibular afferents have not been defined. We treated anesthetized chinchillas with one injection of gentamicin (26.7 mg/ml) into the middle ear and made extracellular recordings from afferents after 5-25 (early) or 90-115 days (late). The relative proportions of regular, intermediate, and irregular afferents did not change after treatment. The spontaneous firing rate of regular afferents was lower (P < 0.001) on the treated side (early: 44.3 +/- 16.3; late: 33.9 +/- 13.2 spikes x s(-1)) than on the untreated side (54.9 +/- 16.8 spikes x s(-1)). Spontaneous rates of irregular and intermediate afferents did not change. The majority of treated afferents did not measurably respond to tilt or rotation (82% in the early group, 76% in the late group). Those that did respond had abnormally low sensitivities (P < 0.001). Treated canal units that responded to rotation had mean sensitivities only 5-7% of the values for untreated canal afferents. Treated otolith afferents had mean sensitivities 23-28% of the values for untreated otolith units. Sensitivity to externally applied galvanic currents was unaffected for all afferents. Intratympanic gentamicin treatment reduced the histological density of all hair cells by 57% (P = 0.04). The density of hair cells with calyx endings was reduced by 99% (P = 0.03), although some remaining hair cells had other features suggestive of type I morphology. Type II hair cell density was not significantly reduced. These findings suggest that a single intratympanic gentamicin injection causes partial damage and loss of vestibular hair cells, particularly type I hair cells or their calyceal afferent endings, does not damage the afferent spike initiation zones, and preserves enough hair cell synaptic activity to drive the spontaneous activity of vestibular afferents.

These data suggest that interictal neurotologic dysfunction in MA and MO share similar features and that the defective oculomotor function is mostly of vestibulocerebellar origin.

Responses of irregularly discharging chinchilla semicircular canal vestibularnerve afferents during high-frequency head rotations. J Neurophysiol 93: 2777-2786, 2005. First published December 15, 2004 doi: 10.1152/jn.01002.2004. Mammalian vestibular-nerve afferents innervating the semicircular canals have been divided into groups according to their discharge regularity, gain at 2-Hz rotational stimulation, and morphology. Low-gain irregular afferents terminate in calyx endings in the central crista, high-gain irregular afferents synapse more peripherally in dimorphic (bouton and calyx) endings, and regular afferents terminate in the peripheral zone as bouton-only and dimorphic endings. The response dynamics of these three groups have been described only up to 4 Hz in previous studies. Reported here are responses of chinchilla semicircular canal vestibular-nerve afferents to rotational stimuli at frequencies up to 16 Hz. The sensitivity of all afferents increased with increasing frequency with the sensitivity of low-gain irregular afferents increasing the most and matching the high-gain irregular afferents at 16 Hz. All afferents increased their phase lead with respect to stimulus velocity at higher frequencies with the highest leads in low-gain irregular afferents and the lowest in regular afferents. No attenuation of sensitivity or shift in phase consistent with the presence of a high-frequency pole over the range tested was noted. Responses were best fit with a torsion-pendulum model combined with a lead operator ( HF1 s ϩ 1)( HF2 s ϩ 1). The discharge regularity of individual afferents was correlated to the value of each afferent's lead operator time constants. These findings suggest that low-gain irregular afferents are well suited for encoding the onset of rapid head movements, a property that would be advantageous for initiation of reflexes with short latency such as the vestibulo-ocular reflex.

Head direction (HD) cells in the rat anterodorsal thalamic nucleus (ADN) fire relative to the animal's directional heading. Lesions of the entire vestibular labyrinth have been shown to severely alter VIIIth nerve input and disrupt these HD signals. To assess the specific contributions of the semicircular canals without altering tonic VIIIth nerve input, ADN cells were recorded from chinchillas after bilateral semicircular canal occlusion. Although ADN HD cells (and also hippocampal place cells and theta cells) were identified in intact chinchillas, no direction-specific activity was seen after canal occlusions. Instead, "bursty" cells were observed that exhibited burst-firing patterns similar to normal HD cells but with firing unrelated to the animal's actual head direction. Importantly, when pairs of bursty cells were recorded, the temporal order of their firing was dependent on the animal's turning direction, as is the case for pairs of normal HD cells. These results suggest that bursty cells are actually disrupted HD cells. The present findings further suggest that the HD cell network is still able to generate spiking activity after canal occlusions, but the semicircular canal input is critical for updating the network activity in register with changes in the animal's HD.