川芎嗪抗链霉素耳毒性作用及其对豚鼠耳蜗外毛细胞钾通道的影响

本文旨在研究川芎嗪（tetramethylpyrazine,TMP）拮抗链霉素耳毒性作用及其对豚鼠耳蜗外毛细胞K^＋通道的影响,探讨TMP拈抗链霉素耳毒性的离子通道机制。60只豚鼠随机分为6组,应用听觉脑干反应（auditory brainstem response,ABR）技术检测豚鼠ABR听阈,观测TMP的抗链霉素耳毒作用;并采用全细胞膜片钳技术观察TMP对耳蜗外毛细胞Ca^2＋敏感艮电流的影响。结果显示,TMP明显降低链霉素导致的豚鼠ABR听阈升高,提示TMP具有抗链霉素耳毒性作用;TMP能明显增大豚鼠耳蜗外毛细胞Ca^2＋敏感艮电流,并呈浓度依赖关系。结果提示,TMP通过增大艮通道电导而拮抗链霉素耳毒性作用。     

虎皮鹦鹉耳蜗感觉细胞的发育与听觉的关系

选用18d、38d、成鸟(3月以上)三种年龄的雄性虎皮鹦鹉作为实验材料,采用测量脑干听觉诱发电位和制作内耳的石蜡切片两种方法,研究了鸟类在发育时期耳蜗感觉上皮细胞的变化以及听觉功能的发育状况。鸟的听觉能力在出生后不断得到提高,38d基本达到成鸟的水平;耳蜗毛细胞的形态、内部结构逐渐趋于成熟,其灵敏度不断提高,感受听觉的能力也在增强,38d基本与成鸟的发育程度相同。耳蜗感觉上皮细胞的发育对听觉行为产生的时间和发展具有极为重要的影响。     

顺铂和噪声联合作用对听觉器官的影响

研究了顺铂与噪声联合作用对耳蜗的毒性,发现联合作用后听阈偏移大于单独顺铂作用后阈移和单独噪声作用后阈移的总和。此外,联合作用后听觉脑干诱发电位振幅下降非常明显。结果表明,顺铂与噪声联合作用对内耳的毒性有协同作用。     

睫状神经营养因子对听觉损伤的保护作用

本研究以耳廓反射、听觉脑干诱发电位、耳蜗生物电和耳蜗铺片组织学检测为指标,观察重组人睫状神经营养因子对豚鼠庆大霉素耳毒性的防治作用。实验结果表明,睫状神经营养因子能减轻庆大霉素对耳蜗及听神经的损害,具有保护听觉功能的作用。     

听觉反馈与鸣禽鸣唱学习可塑性

对近年来听觉反馈在鸣禽鸣唱学习可塑性方面的研究进行综述．鸣禽的鸣曲学习与人类的语言学习都是一种依赖于听觉反馈的模仿学习．在鸣曲学习过程中,幼鸟根据听觉反馈的信息对鸣曲进行比较和修正,使其不断完善;在鸣曲维持过程中,成鸟通过听觉反馈实时监测自己鸣曲的完整性与准确性,使鸣曲保持稳定．鸣曲的输出与听觉反馈信息在鸟脑中得到整合,并指导下一次鸣唱做出适当的调整．近年来,这种感觉与运动信息在鸣禽发声核团中的整合机制逐渐引起了国内外研究者的兴趣．其中,新纹状体巨细胞核外侧部(LMAN)神经元对自鸣曲(BOS)高度选择性的听觉应答在鸣曲去稳定化过程中的作用,以及高级发声中枢(HVC)中镜像神经元的发现,为今后的研究提供了重要的线索．     

电码针对庆大霉素耳中毒的防治作用及其机制的研究

目的：观察电码针对豚鼠庆大霉素（GE）耳毒性的防治作用,方法：测定脑干听觉诱发电位（BAEP）和用组织化学方法测定耳蝇毛细胞及血管纹的琥珀酸脱氢酶（SDH）。结果：电针能降低CE引起的BAEP反应阈的上升幅度,缩小BAEP波峰潜伏期及波峰间期的延长;能保护毛细胞及耳蜗血管纹细胞线粒体呼吸酶的活性。结论：电针能降低GE5的耳毒性,保护毛细胞及耳蜗血管纹细胞线粒体酶的活性。保证这些细胞能量代谢,维持细胞所需要能量的各种功能的活动。减少细胞的损伤,可能有是电针防治GE耳毒性的机制之一。     

鸣禽控制发声核团和脑干听觉核团及神经通路的综合研究

采用辣根过氧化物酶顺、逆行标记方法对鸣禽鸟蜡嘴雀控制发声的神经核团、脑干听觉核团及神经通路,从外周至中枢逐级进行了追踪研究。结果表明：１．控制发声的神经核团及通路,前脑古纹状体腹内侧粗核是大脑控制发声的重要核团之一,它发出枕中脑后束经端脑前联合呈双侧支配延脑中间核,中间核又发出舌下神经经气管鸣管分支支配鸣肌,中间核同时也接受中脑背内侧核的支配,２．脑干听觉中枢及通路,中脑背外侧核是脑干较高级听觉中枢、初级中枢耳蜗核由角核和前庭外侧核组成,ＮＡ发出以对侧为主的纤维经外侧丘系可直接传入中脑背外侧核形成脑干听觉直接通路。     

鸣禽控制发声核团和脑干听觉核团及神经通路…

采用辣根过氧化物酶顺、逆行标记方法对鸣禽鸟蜡嘴雀控制发声的神经核团、脑干听觉核团及神经通路,从外周至中枢逐级进行了追踪研究。结果表明：１．控制发声的神经核团及通路,前脑古纹状体腹内侧粗核是大脑控制发声的重要核团之一,它发出枕中脑后束经端脑前联合呈双侧支配延脑中间核,中间核又发出舌下神经经气管鸣管分支支配鸣肌,中间核同时也接受中脑背内侧核的支配;２．脑干听觉中枢及通路,中脑背外侧核是脑干较高级听觉中     

脑细胞生长肽对GM耳毒性的预防作用

目的：观察脑细胞生长肽（cerebral cell growth peptide,CCGP)对庆大霉素（gentamicin,GM)引起的豚鼠耳中毒的预防作用）。方法：用脑干听觉诱发电位（brainstem auditory evoked potential,BAEP)和组织化学方法分别检测动物听阀的变化和耳蜗毛细胞线粒体内琥珀酸脱氢酶（succinate dehydrogenase,SDH)及溶酶体内的酸性磷酸酶（acid phosphatase,ACP)活性变化,并在三组动物进行耳蜗受损毛细胞计数。结果：CCGP能降低GM引起的BAEP反应阈的上升幅度,保护耳蜗毛细胞SDH和维持溶酶体的完整性,减轻毛细胞的损伤。结论：CCGP能降低GM的中毒性;保护耳蜗毛细胞SDH,维持毛细胞的能量代谢,减少溶酶体损伤,降低溶酶体内水解酶逸出引起的毛细胞自溶性损伤,可能是CCGP预防GM耳毒性的机制之一。     

电针对庆大霉素耳毒性的预防作用

目的和方法 :本实验用耳廓反射 (PR)、脑干听觉诱发电位 (BAEP)、组织化学方法 ,观察电针疗法对豚鼠庆大霉素 (GE)耳毒性的防治作用 ,并探讨其机制。结果 :电针疗法能降低GE引起的PR阈值和BAEP反应阈的上移幅度及BAEP波峰潜伏期和波峰间期的延长 ,能维持毛细胞溶酶体的完整 ,防止毛细胞的自溶性破坏。结论 :电针疗法有对抗GE耳毒性作用。维持耳蜗毛细胞内溶酶体完整 ,防止溶酶体内水解酶的逸出而发生细胞自溶 ,可能是电针疗法的作用机制之一。     

Behavioral and physiological studies of hearing in birds.

Studies of hearing thresholds and frequency- and intensity-difference limens for birds are reviewed. Where possible these are related to limitations placed on auditory function by stimulus processing at peripheral levels of the avian auditory system. The high frequency limit of bird hearing is about 10 kHz; this limit is shown to be imposed in part by middle ear function and in part by cochlear mechanisms. For frequencies greater than 1.0 kHz, frequency-difference limens (DLs) show a similar dependence on frequency in birds as in mammals. Correspondingly, cochlear filtering is shown to be as good in birds as in mammals. At frequency below 1.0 kHz, frequency DLs in birds are poorer than in mammals. These low frequency differences may not be attributable to peripheral processing. Intensity-difference limens are worse in birds than mammals; there seem to be no differences in peripheral processing between birds and mammals which can account for this behavioral difference. Finally, complexities in processing at higher levels of the avian auditory system which have been related to detection of species-specific vocalizations are shown to appear in the first brainstem auditory nuclei.     

Encoding of phase spectra by the peripheral auditory system of the bullfrog

In this study we have examined the sensitivity of auditory nerve fibers in the bullfrog (Rana catesbeiana) to changes in the phase spectrum of an equal-amplitude multi-harmonic stimulus which spanned the bullfrog's range of hearing. To assess peripheral auditory phase sensitivity, changes in the response properties of VIIIth nerve fibers were measured when the relative phase angle of a single harmonic component nearest a unit's best excitatory frequency was systematically varied. The results revealed that shifts in the phase spectrum are encoded in at least J different ways by the peripheral auditory system of the bullfrog: 1) by changes in the degree of spike synchronization of fibers from both inner ear organs (the amphibian papilla and the basilar papilla) to the fundamental waveform period; 2) by changes in the shapes of period histograms of fibers from both organs; and 3) by changes in the spike rates of amphibian papilla fibers. The presence of phase sensitivity in the peripheral auditory system of the bullfrog indicates that information regarding the fine-temporal waveshape and the underlying phase spectrum of an acoustic signal is contained within the spike trains of VIIIth nerve fibers. Similar sensitivities to changes in the phase spectra and temporal waveshapes of acoustic signals may also be present in the peripheral auditory system of other vertebrates. Such studies could provide valuable insight into the role that phase spectra and temporal waveshape may play in bioacoustic communication.Abbreviations BEF best excitatory frequency - BEC best excitatory component - CS_{f 1} synchronization to the fundamental period Portions of this study have been summarized in abstract form (Bodnar and Capranica 1991)     

Aminoglycosides block the Kv3.1 potassium channel and reduce the ability of inferior colliculus neurons to fire at high frequencies

The Kv3.1 potassium channel is expressed at high levels in auditory nuclei and contributes to the ability of auditory neurons to fire at high frequencies. We have tested the effects of streptomycin, an agent that produces progressive hearing loss, on the firing properties of inferior colliculus neurons and on Kv3.1 currents in transfected cells. We found that in inferior colliculus neurons, intracellular streptomycin decreased the current density of a high threshold, noninactivating outward current and reduced the rate of repolarization of action potentials and the ability of these neurons to fire at high frequencies. Furthermore, potassium current in CHO cells transfected with the Kv3.1 gene was reduced by 50% when cells were cultured in the presence of streptomycin or when streptomycin was introduced intracellularly in the pipette solution. In the presence of intracellular streptomycin, the activation rate of Kv3.1 current increased and inhibition by extracellular TEA become voltage-dependent. The data indicate that streptomycin inhibits Kv3.1 currents by inducing a conformational change in the Kv3.1 channel. The hearing loss caused by aminoglycoside antibiotics may be partially mediated by their inhibition of Kv3.1 current in auditory neurons.     

Visual advantage in deaf adults linked to retinal changes

The altered sensory experience of profound early onset deafness provokes sometimes large scale neural reorganisations. In particular, auditory-visual cross-modal plasticity occurs, wherein redundant auditory cortex becomes recruited to vision. However, the effect of human deafness on neural structures involved in visual processing prior to the visual cortex has never been investigated, either in humans or animals. We investigated neural changes at the retina and optic nerve head in profoundly deaf (N = 14) and hearing (N = 15) adults using Optical Coherence Tomography (OCT), an in-vivo light interference method of quantifying retinal micro-structure. We compared retinal changes with behavioural results from the same deaf and hearing adults, measuring sensitivity in the peripheral visual field using Goldmann perimetry. Deaf adults had significantly larger neural rim areas, within the optic nerve head in comparison to hearing controls suggesting greater retinal ganglion cell number. Deaf adults also demonstrated significantly larger visual field areas (indicating greater peripheral sensitivity) than controls. Furthermore, neural rim area was significantly correlated with visual field area in both deaf and hearing adults. Deaf adults also showed a significantly different pattern of retinal nerve fibre layer (RNFL) distribution compared to controls. Significant correlations between the depth of the RNFL at the inferior-nasal peripapillary retina and the corresponding far temporal and superior temporal visual field areas (sensitivity) were found. Our results show that cross-modal plasticity after early onset deafness may not be limited to the sensory cortices, noting specific retinal adaptations in early onset deaf adults which are significantly correlated with peripheral vision sensitivity.     

Morphological and physiological differences of the auditory system in three related bushcrickets (Orthoptera: Phaneropteridae, Poecilimon)

Abstract. The auditory system of three closely related bushcrickets was investigated with respect to morphological and physiological differences. The size of the acoustic vesicle in the prothorax cavity and the size of the acoustic spiracle were compared to differences in auditory tuning of the tympanic nerve and differences in the directionality. The results indicate that a small auditory vesicle and auditory spiracle provide reduced sensitivity in the high frequency range (above 10—15 kHz), but increase sensitivity at low frequencies (below 10 kHz). The directionality of the hearing system deteriorates at frequencies between 10 and 25 kHz in species with a small spiracle and trachea. The evolutionary implications of these differences of the auditory systems are discussed. They are considered to be influenced more by ecological factors than bioacoustical ones.     

The detrimental effects of potassium bromate and thioglycolate on auditory brainstem response of guinea pigs

Potassium bromate (KBrO3) is known to be an oxidizing agent that is used not only as a food additive, mainly in the bread-making process, but also as a neutralizer in thioglycolate containing hair curling set. Although it has been shown that bromate poisoning could cause severe and irreversible sensorineural hearing loss as well as renal failure, the action mechanism of bromate-induced otoneurotoxicity especially its combination with thioglycolate remains to be studied. In this study, we attempted to investigate the toxic effects of KBrO3 in combination with or without thioglycolate on the auditory brainstem response (ABR) system in the guinea-pigs which was claimed to be very susceptible to the xenobiotics. In a preliminary test, we have found that after consecutive 2 weeks administration, KBrO3 caused a significant prolongation of wave I-III and the interwave latencies of ABR as well as significantly elevated the threshold of hearing, suggesting that the conduction velocity of the peripheral auditory nerve was delayed. By contrast, the absolute latency of wave IV/V and the interwave latency of wave III-V were not significantly prolonged, suggesting that KBrO3 had no effect on the brainstem. This oto-neurotoxic effect of KBrO3 was markedly enhanced by combining with thioglycolate. Our data also indicated that KBrO3 combined with thioglycolate but not KBrO3 alone prominantly caused a decrease of body weight. However, enzymatic activities (including Na+/K+-ATPase and Ca2+-ATPase) and the level of nitric oxide (NO) was significantly affected in the brainstem. Based on these findings, we tentatively conclude that whether KBrO3 alone or KBrO3 combined with thioglycolate induced oto-neurotoxicity majorly through the peripheral auditory nerve rather than via the central brainstem intoxication.     

The auditory system of non-calling grasshoppers (Melanoplinae: Podismini) and the evolutionary regression of their tympanal ears

Reduction of tympanal hearing organs is repeatedly found amongst insects and is associated with weakened selection for hearing. There is also an associated wing reduction, since flight is no longer required to evade bats. Wing reduction may also affect sound production. Here, the auditory system in four silent grasshopper species belonging to the Podismini is investigated. In this group, tympanal ears occur but sound signalling does not. The tympanal organs range from fully developed to remarkably reduced tympana. To evaluate the effects of tympanal regression on neuronal organisation and auditory sensitivity, the size of wings and tympana, sensory thresholds and sensory central projections are compared. Reduced tympanal size correlates with a higher auditory threshold. The threshold curves of all four species are tuned to low frequencies with a maximal sensitivity at 3–5 kHz. Central projections of the tympanal nerve show characteristics known from fully tympanate acridid species, so neural elements for tympanal hearing have been strongly conserved across these species. The results also confirm the correlation between reduction in auditory sensitivity and wing reduction. It is concluded that the auditory sensitivity of all four species may be maintained by stabilising selective forces, such as predation.     

Parallel evolution of auditory genes for echolocation in bats and toothed whales

The ability of bats and toothed whales to echolocate is a remarkable case of convergent evolution. Previous genetic studies have documented parallel evolution of nucleotide sequences in Prestin and KCNQ4, both of which are associated with voltage motility during the cochlear amplification of signals. Echolocation involves complex mechanisms. The most important factors include cochlear amplification, nerve transmission, and signal re-coding. Herein, we screen three genes that play different roles in this auditory system. Cadherin 23 (Cdh23) and its ligand, protocadherin 15 (Pcdh15), are essential for bundling motility in the sensory hair. Otoferlin (Otof) responds to nerve signal transmission in the auditory inner hair cell. Signals of parallel evolution occur in all three genes in the three groups of echolocators--two groups of bats (Yangochiroptera and Rhinolophoidea) plus the dolphin. Significant signals of positive selection also occur in Cdh23 in the Rhinolophoidea and dolphin, and Pcdh15 in Yangochiroptera. In addition, adult echolocating bats have higher levels of Otof expression in the auditory cortex than do their embryos and non-echolocation bats. Cdh23 and Pcdh15 encode the upper and lower parts of tip-links, and both genes show signals of convergent evolution and positive selection in echolocators, implying that they may co-evolve to optimize cochlear amplification. Convergent evolution and expression patterns of Otof suggest the potential role of nerve and brain in echolocation. Our synthesis of gene sequence and gene expression analyses reveals that positive selection, parallel evolution, and perhaps co-evolution and gene expression affect multiple hearing genes that play different roles in audition, including voltage and bundle motility in cochlear amplification, nerve transmission, and brain function.     

An exception to the matched filter hypothesis: A mismatch of male call frequency and female best hearing frequency in a torrent frog

The matched filter hypothesis proposes that the tuning of auditory sensitivity and the spectral character of calls will match in order to maximize auditory processing efficiency during courtship. In this study, we analyzed the acoustic structure of male calls and both male and female hearing sensitivities in the little torrent frog (Amolops torrentis), an anuran species who transmits acoustic signals across streams. The results were in striking contradiction to the matched filter hypothesis. Auditory brainstem response results showed that the best hearing range was 1.6–2 kHz consistent with the best sensitive frequency of most terrestrial lentic taxa, yet completely mismatched with the dominant frequency of conspecific calls (4.3 kHz). Moreover, phonotaxis tests show that females strongly prefer high‐frequency (4.3 kHz) over low‐frequency calls (1.6 kHz) regardless of ambient noise levels, although peripheral auditory sensitivity is highest in the 1.6–2 kHz range. These results are consistent with the idea that A. torrentis evolved from nonstreamside species and that high‐frequency calls evolved under the pressure of stream noise. Our results also suggest that female preferences based on central auditory system characteristics may evolve independently of peripheral auditory system sensitivity in order to maximize communication effectiveness in noisy environments.     

Loss of Central Auditory Processing in a Mouse Model of Canavan Disease

Canavan Disease (CD) is a leukodystrophy caused by homozygous null mutations in the gene encoding aspartoacylase (ASPA). ASPA-deficiency is characterized by severe psychomotor retardation, and excessive levels of the ASPA substrate N-acetylaspartate (NAA). ASPA is an oligodendrocyte marker and it is believed that CD has a central etiology. However, ASPA is also expressed by Schwann cells and ASPA-deficiency in the periphery might therefore contribute to the complex CD pathology. In this study, we assessed peripheral and central auditory function in the Aspa^lacZ/lacZ rodent model of CD using auditory brainstem response (ABR). Increased ABR thresholds and the virtual loss of waveform peaks 4 and 5 from Aspa^lacZ/lacZ mice, indicated altered central auditory processing in mutant mice compared with Aspa^wt/wt controls and altered central auditory processing. Analysis of ABR latencies recorded from Aspa^lacZ/lacZ mice revealed that the speed of nerve conduction was unchanged in the peripheral part of the auditory pathway, and impaired in the CNS. Histological analyses confirmed that ASPA was expressed in oligodendrocytes and Schwann cells of the auditory system. In keeping with our physiological results, the cellular organization of the cochlea, including the organ of Corti, was preserved and the spiral ganglion nerve fibres were normal in ASPA-deficient mice. In contrast, we detected substantial hypomyelination in the central auditory system of Aspa^lacZ/lacZ mice. In summary, our data suggest that the lack of ASPA in the CNS is responsible for the observed hearing deficits, while ASPA-deficiency in the cochlear nerve fibres is tolerated both morphologically and functionally.