The sensory hair cells of the inner ear undergo apoptosis after acoustic trauma or aminoglycoside antibiotic treatment, causing permanent auditory and vestibular deficits in humans. Previous studies have demonstrated a role for caspase activation in hair cell death and ototoxic injury that can be reduced by concurrent treatment with caspase inhibitors in vitro. In this study, we examined the protective effects of caspase inhibition on hair cell death in vivo after systemic injections of aminoglycosides. In one series of experiments, chickens were implanted with osmotic pumps that administrated the pan-caspase inhibitor z-Val-Ala-Asp(Ome)-fluoromethylketone (zVAD) into inner ear fluids. One day after the surgery, the animals received a 5 d course of treatment with streptomycin, a vestibulotoxic aminoglycoside. Direct infusion of zVAD into the vestibule significantly increased hair cell survival after streptomycin treatment. A second series of experiments determined whether rescued hair cells could function as sensory receptors. Animals treated with streptomycin displayed vestibular system impairment as measured by a greatly reduced vestibulo-ocular response (VOR). In contrast, animals that received concurrent systemic administration of zVAD with streptomycin had both significantly greater hair cell survival and significantly increased VOR responses, as compared with animals treated with streptomycin alone. These findings suggest that inhibiting the activation of caspases promotes the survival of hair cells and protects against vestibular function deficits after aminoglycoside treatment.

Rotational head motion in vertebrates is detected by the three semicircular canals of the vestibular system whose innervating primary afferent fibers encode movement information in specific head planes. In order to further investigate the nature of vestibular central processing of rotational motion in rhesus monkeys, it was first necessary to quantify afferent information coding in this species. Extracellular recordings were performed to determine the spatial and dynamic properties of semicircular canal afferents to rotational motion in awake rhesus monkeys. We found that the afferents innervating specific semicircular canals had maximum sensitivity vectors that were mutually orthogonal. Similar to other species, afferent response dynamics varied, with regular firing afferents having increased long time constants ( t(1)), decreased cupula velocity time constants ( t(v)), and decreased fractional order dynamic operator values ( s(k)) as compared to irregular firing afferents.

Haque, Asim and J. David Dickman. Vestibular gaze stabilization: different behavioral strategies for arboreal and terrestrial avians. J Neurophysiol 93: 1165-1173, 2005. First published November 3, 2004 doi:10.1152/jn.00966.2004. In birds, it is thought that head movements play a major role in the reflexive stabilization of gaze and vision. In this study, we investigated the contributions of the eye and head to gaze stabilization during rotations under both head-fixed [vestibuloocular (VOR)] and headfree conditions in two avian species: pigeons and quails. These two species differ both in ocular anatomy (the pigeon has 2 distinct foveal regions), as well as in behavioral repertoires. Pigeons are arboreal, fly extended distances, and can navigate. Quails are primarily engrossed in terrestrial niches and fly only short distances. Unlike the head-fixed VOR gains that were under-compensatory for both species, gaze gains under head-free conditions were completely compensatory at high frequencies. This compensation was achieved primarily with head movements in pigeons, but with combined head and eye-in-head contributions in the quail. In contrast, eye-in-head motion, which was significantly reduced for head-free compared with head-fixed conditions, contributed very little to overall gaze stability in pigeons. These results suggest that disparity between the stabilization strategies employed by these two birds may be attributed to differences in species-specific behavior and anatomy.