Loud sound-induced changes in cochlear mechanics.
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To investigate the inner ear response to intense sound and the mechanisms behind temporary threshold shifts, anesthetized guinea pigs were exposed to tones at 100-112 dB SPL. Basilar membrane vibration was measured using laser velocimetry, and the cochlear microphonic potential, compound action potential of the auditory nerve, and local electric AC potentials in the organ of Corti were used as additional indicators of cochlear function. After exposure to a 12-kHz intense tone, basilar membrane vibrations in response to probe tones at the characteristic frequency of the recording location (17 kHz) were transiently reduced. This reduction recovered over the course of 50 ms in most cases. Organ of Corti AC potentials were also reduced and recovered with a time course similar to the basilar membrane. When using a probe tone at either 1 or 4 kHz, organ of Corti AC potentials were unaffected by loud sound, indicating that transducer channels remained intact. In most experiments, both the basilar membrane and the cochlear microphonic response to the 12-kHz overstimulation was constant throughout the duration of the intense stimulus, despite a large loss of cochlear sensitivity. It is concluded that the reduction of basilar membrane velocity that followed loud sound was caused by changes in cochlear amplification and that the cochlear response to intense stimulation is determined by the passive mechanical properties of the inner ear structures. (+info)
Internal shearing within the hearing organ evoked by basilar membrane motion.
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The vibration of the hearing organ that occurs during sound stimulation is based on mechanical interactions between different cellular structures inside the organ of Corti. The exact nature of these interactions is unclear and subject to debate. In this study, dynamic structural changes were produced by stepwise alterations of scala tympani pressure in an in vitro preparation of the guinea pig temporal bone. Confocal images were acquired at each level of pressure. In this way, the motion of several structures could be observed simultaneously with high resolution in a nearly intact system. Images were analyzed using a novel wavelet-based optical flow estimation algorithm. Under these conditions, the reticular lamina moved as a stiff plate with a center of rotation in the region of the inner hair cells. Despite being enclosed in several types of supporting cells, the inner hair cells, together with the adjacent inner pillar cells, moved in a manner signifying high compliance. The outer hair cells displayed radial motion indicative of cellular bending. Together, these results show that shearing motion occurs between several parts of the organ, and that structural relationships within the organ change dynamically during displacement of the basilar membrane. (+info)
The zinc finger transcription factor Gfi1, implicated in lymphomagenesis, is required for inner ear hair cell differentiation and survival.
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Gfi1 was first identified as causing interleukin 2-independent growth in T cells and lymphomagenesis in mice. Much work has shown that Gfi1 and Gfi1b, a second mouse homolog, play pivotal roles in blood cell lineage differentiation. However, neither Gfi1 nor Gfi1b has been implicated in nervous system development, even though their invertebrate homologues, senseless in Drosophila and pag-3 in C. elegans are expressed and required in the nervous system. We show that Gfi1 mRNA is expressed in many areas that give rise to neuronal cells during embryonic development in mouse, and that Gfi1 protein has a more restricted expression pattern. By E12.5 Gfi1 mRNA is expressed in both the CNS and PNS as well as in many sensory epithelia including the developing inner ear epithelia. At later developmental stages, Gfi1 expression in the ear is refined to the hair cells and neurons throughout the inner ear. Gfi1 protein is expressed in a more restricted pattern in specialized sensory cells of the PNS, including the eye, presumptive Merkel cells, the lung and hair cells of the inner ear. Gfi1 mutant mice display behavioral defects that are consistent with inner ear anomalies, as they are ataxic, circle, display head tilting behavior and do not respond to noise. They have a unique inner ear phenotype in that the vestibular and cochlear hair cells are differentially affected. Although Gfi1-deficient mice initially specify inner ear hair cells, these hair cells are disorganized in both the vestibule and cochlea. The outer hair cells of the cochlea are improperly innervated and express neuronal markers that are not normally expressed in these cells. Furthermore, Gfi1 mutant mice lose all cochlear hair cells just prior to and soon after birth through apoptosis. Finally, by five months of age there is also a dramatic reduction in the number of cochlear neurons. Hence, Gfi1 is expressed in the developing nervous system, is required for inner ear hair cell differentiation, and its loss causes programmed cell death. (+info)
Coding of sound intensity in the chick cochlear nerve.
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Tuning curves, spontaneous activity, and rate-intensity (RI) functions were obtained from units in the chick cochlear nerve. The characteristic frequency (CF) was determined from each tuning curve. The shape of each RI function was subjectively evaluated and assigned to one of four RI types. The breakpoint, discharge rate at the highest SPLs, and slopes of the primary and secondary segments were quantified for each function. The CF and RI type were then related to these variables. A new RI function was observed in which the discharge activity in the secondary segment diminished as stimulus level increased above the breakpoint. This function was called a "sloping-down" type. In 959 units, saturating, sloping-up, sloping-down, and straight RI types were identified in 39.2, 35.5, 12.6, and 12.7% of the sample, respectively. The slope of the primary segment was nearly the same in each of the four types and averaged 5.48 S. s(-1). dB(-1) across all units. The slopes of the secondary segments formed four groupings when segregated by RI type based on the subjective assignments and averaged 0.03, 1.22, -0.90, and 3.95 S. s(-1). dB(-1) in the saturating, sloping-up, sloping-down, and straight types, respectively. The data describing the secondary segments of all units were fit with a multi-compartment polynomial and showed a continuous distribution that segregated, with some overlap, into the different RI categories. The proportion of RI types, as well as the secondary and primary slopes were approximately constant across CFs. In addition, it would appear that the other parameters that define the four types were, for the most part, homogeneously distributed across the frequency axis of the chick inner ear. Finally, a comparison of RI functions having a common CF suggested that the compressive nonlinearity that determines RI type may be a phenomenon localized to individual hair cells in the bird ear. (+info)
Efferent protection from acoustic injury is mediated via alpha9 nicotinic acetylcholine receptors on outer hair cells.
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Exposure to intense sound can damage the mechanosensors of the inner ear and their afferent innervation. These neurosensory elements are innervated by a sound-activated feedback pathway, the olivocochlear efferent system. One major component of this system is cholinergic, and known cholinergic effects are mediated by the alpha9/alpha10 nicotinic acetylcholine receptor (nAChR) complex. Here, we show that overexpression of alpha9 nAChR in the outer hair cells of bacterial artificial chromosome transgenic mice significantly reduces acoustic injury from exposures causing either temporary or permanent damage, without changing pre-exposure cochlear sensitivity to low- or moderate-level sound. These data demonstrate that efferent protection is mediated via the alpha9 nAChR in the outer hair cells and provide direct evidence for a protective role, in vivo, of a member of the nAChR family. (+info)
Reduction in sharpness of frequency tuning but not endocochlear potential in aging and noise-exposed BALB/cJ mice.
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Schuknecht proposed categories for human age-related hearing loss (ARHL) based upon whether the primary degeneration involves the organ of Corti (sensory ARHL), spiral ganglion cells (neural), stria vascularis (strial), or a combination of these (mixed). Genetically standardized mouse ARHL models can help validate Schuknecht's framework and clarify the underlying cellular processes. Much recent work has focused on the mouse Ahl locus, which promotes both ARHL and noise-induced hearing loss. On the C57BL/6 inbred background, Ahl has been associated with degeneration of organ of Corti, afferent neurons, and stria vascularis/spiral ligament, suggesting that it promotes mixed (sensory/neural/strial) ARHL. Some cochlear degeneration in C57BL/6 mice could be caused by genes other than Ahl, however. The question of what constitutes Ahl-related pathology can be addressed by comparing C57BL/6 mice with other strains that carry the same allele, including BALB/c substrains. We examined the effects of aging and broadband noise exposure in inbred BALB/cJ mice (1.5-13.0 mos) using measures of frequency tuning (compound action potential tuning curves) (CAPTCs), strial function (endocochlear potential recording, EP), and light microscopy. Aging and noise led to generally similar physiological and anatomical changes. Reductions in sensitivity and sharpness of frequency tuning were not consistently linked to hair cell loss, reduction in the EP, or changes in the lateral wall. Instead they appeared best explained by alterations in supporting cells in the basal half of the cochlear and in the spiral limbus in the apex. These results emphasize the importance of cell types other than hair cells in cochlear pathology. They also indicate that Ahl does not necessarily promote a strial form of ARHL. (+info)
Variation in large-conductance, calcium-activated potassium channels from hair cells along the chicken basilar papilla.
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The mechanism for electrical tuning in non-mammalian hair cells rests within the widely diverse kinetics of functionally distinct, large-conductance potassium channels (BK), thought to result from alternative splicing of the pore-forming alpha subunit and variable co-expression with an accessory beta subunit. Inside-out patches from hair cells along the chicken basilar papilla revealed 'tonotopic' gradations in calcium sensitivity and deactivation kinetics. The resonant frequency for the hair cell from which the patch was taken was estimated from deactivation rates, and this frequency reasonably matched that predicted from the originating cell's tonotopic location. The rates of deactivation for native BK channels were much faster than rates reported for cloned chicken BK channels including both alpha and beta subunits. This result was surprising since patches were pulled from hair cells in the apical half of the papilla where beta subunits are most highly expressed. Heterogeneity in the properties of native chicken BK channels implies a high degree of molecular variation and hinders our ability to identify those molecular constituents. (+info)
Identification and characterization of a novel mouse plexin, plexin-A4.
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Plexins belonging to the plexin-A subfamily form complexes with neuropilins and propagate signals of class 3 semaphorins into neurons, even though they do not directly bind the semaphorins. In this study, we identified a new member of the plexin-A subfamily in the mice, plexin-A4, and showed that it was expressed in the developing nervous system with a pattern different to that of other members of the plexin-A subfamily (plexin-A1, plexin-A2 and plexin-A3). COS-7 cells coexpressing plexin-A4 with neuropilin-1 were induced to contract by Sema3A, a member of the class 3 semaphorin. Ectopic expression of plexin-A4 in mitral cells that are originally insensitive to Sema3A resulted in the collapse of growth cones in the presence of Sema3A. These results suggest that plexin-A4 plays a role in the propagation of Sema3A activities. (+info)