Noise-induced tinnitus is generally associated with hearing impairment caused by traumatic acoustic overexposure. Previous studies in laboratory animals and human subjects, however, have observed differences in tinnitus susceptibility, even among individuals with similar hearing loss. The mechanisms underlying increased sensitivity or, conversely, resistance to tinnitus are still incompletely understood. Here, we used behavioral tests and ABR audiometry to compare the sound-evoked responses of mice that differed in the presence of noise-induced tinnitus. The aim was to find a specific pre-exposure neurophysiological marker that would predict the development of tinnitus after acoustic trauma. Noise-exposed mice were screened for tinnitus-like behavior with the GPIAS paradigm and subsequently divided into tinnitus (+T) and non-tinnitus (-T) groups. Both groups showed hearing loss after exposure, manifested by elevated audiometric thresholds along with reduced amplitudes and prolonged latencies of ABR waves. Prior to exposure, except for a slightly increased slope of growth function for ABR amplitudes in +T mice, the two groups did not show significant audiometric differences. Behavioral measures, such as the magnitude of the acoustic startle response and its inhibition by gap pre-pulse, were also similar before exposure in both groups. However, +T mice showed significantly increased suppression of the acoustic startle response in the presence of background noise of moderate intensity. Thus, increased modulation of startle by background sounds may represent a behavioral correlate of susceptibility to noise-induced tinnitus, and its measurement may form the basis of a simple non-invasive method for predicting tinnitus development in laboratory rodents.
- Publikační typ
- časopisecké články MeSH
The cranial window technique has proven to be an effective method for in vivo imaging of cortical activity. However, given the invasive nature of this procedure, possible side effects could be expected in the nervous system. In this study, we evaluated the effects of unilateral cranial window surgery on auditory function in C57BL6 mice using electrophysiological and behavioral approaches. We found that one week after implantation, mice exhibited both increased thresholds and decreased amplitudes of their auditory brainstem responses. These changes were accompanied by a decrease in distortion product otoacoustic emissions, indicating a deterioration in cochlear function. In addition, behavioral testing of these mice revealed reduced suppression of their acoustic startle response by gap prepulse, suggesting a deficit in auditory processing or possibly the presence of tinnitus. The changes in auditory function appeared to be only partially reversible within four weeks after surgery. Thus, our findings suggest that cranial window implantation causes long-term functional changes in the auditory system that should be considered when interpreting data from optical imaging techniques.
Usher syndrome (USH) is the most common form of monogenic deaf-blindness. Loss of vision is untreatable and there are no suitable animal models for testing therapeutic strategies of the ocular constituent of USH, so far. By introducing a human mutation into the harmonin-encoding USH1C gene in pigs, we generated the first translational animal model for USH type 1 with characteristic hearing defect, vestibular dysfunction, and visual impairment. Changes in photoreceptor architecture, quantitative motion analysis, and electroretinography were characteristics of the reduced retinal virtue in USH1C pigs. Fibroblasts from USH1C pigs or USH1C patients showed significantly elongated primary cilia, confirming USH as a true and general ciliopathy. Primary cells also proved their capacity for assessing the therapeutic potential of CRISPR/Cas-mediated gene repair or gene therapy in vitro. AAV-based delivery of harmonin into the eye of USH1C pigs indicated therapeutic efficacy in vivo.
Inhibitory circuits in the auditory brainstem undergo multiple postnatal changes that are both activity-dependent and activity-independent. We tested to see if the shift from GABA- to glycinergic transmission, which occurs in the rat medial nucleus of the trapezoid body (MNTB) around the onset of hearing, depends on sound-evoked neuronal activity. We prevented the activity by bilateral cochlear ablations in early postnatal rats and studied ionotropic GABA and glycine receptors in MNTB neurons after hearing onset. The removal of the cochlea decreased responses of GABAA and glycine receptors to exogenous agonists as well as the amplitudes of inhibitory postsynaptic currents. The reduction was accompanied by a decrease in the number of glycine receptor- or vesicular GABA transporter-immunopositive puncta. Furthermore, the ablations markedly affected the switch in presynaptic GABAA to glycine receptors. The increase in the expression of postsynaptic glycine receptors and the shift in inhibitory transmitters were not prevented. The results suggest that inhibitory transmission in the MNTB is subject to multiple developmental signals and support the idea that auditory experience plays a role in the maturation of the brainstem glycinergic circuits.
- MeSH
- ablace * MeSH
- corpus trapezoideum fyziologie MeSH
- inhibiční postsynaptické potenciály fyziologie MeSH
- kochlea patofyziologie chirurgie MeSH
- krysa rodu rattus MeSH
- nervový přenos * MeSH
- nervový útlum účinky léků fyziologie MeSH
- novorozená zvířata MeSH
- receptory GABA-A - agonisté farmakologie MeSH
- receptory GABA-A fyziologie MeSH
- receptory glycinu agonisté metabolismus fyziologie MeSH
- sluchové kmenové evokované potenciály fyziologie MeSH
- transportéry VIAAT metabolismus MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
