In mice, the auditory brainstem response (ABR) is frequently used to assess hearing status in transgenic hearing models. The diagnostic value of the ABR depends on knowledge about the anatomical sources of its characteristic waves. Here, we studied the contribution of the inferior colliculus (IC) to the click-evoked scalp ABR in mice. We demonstrate a non-invasive correlate of the IC response that can be measured in the scalp ABR as a slow positive wave P with peak latency 7-8 ms when recorded with adequate band-pass filtering. Wave P showed close correspondence in latency, magnitude and shape with the sustained part of evoked spiking activity and local field potentials (LFP) in the central nucleus of the IC. In addition, the onset peaks of the IC response were related temporally to ABR wave V and to some extent to wave IV. This relation was further supported by depth-dependent modulation of the shape of ABR wave IV and V within the IC suggesting generation within or in close vicinity to the IC. In conclusion, the slow ABR wave P in the scalp ABR may represent a complementary non-invasive marker for IC activity in the mouse. Further, the latency of synchronized click-evoked activity in the IC supports the view that IC contributes to ABR wave V, and possibly also to ABR wave IV.
Eustachian tube disorders can lead to chronic otitis media with consecutive conductive hearing loss. To improve treatment and to develop new types of implants such as stents, an adequate experimental animal model is required. As the middle ear of sheep is known to be comparable to the human middle ear, the dimensions of the Eustachian tube in two strains of sheep were investigated. The Eustachian tube and middle ear of half heads of heathland and blackface sheep were filled with silicone rubber, blended with barium sulfate to induce X-ray visibility. Images were taken by digital volume tomography. The tubes were segmented, and a three-dimensional model of every Eustachian tube was generated. The lengths, diameters and shapes were determined. Additionally, the feasibility of endoscopic stent implantation and fixation was tested in cadaver experiments. The length of the tube between ostium pharyngeum and the isthmus and the diameters were comparable to published values for the human tube. The tube was easily accessible through the nose, and then stents could be implanted and fixed at the isthmus. The sheep appears to be a promising model for testing new stent treatments for middle ear ventilation disorders.
Hearing depends on the transduction of sounds into neural signals by the inner hair cells of the cochlea. Cochleae also have outer hair cells with unique electromotile properties that increase auditory sensitivity, but they are particularly susceptible to damage by intense noise exposure, ototoxic drugs, and aging. Although the outer hair cells have synapses on afferent neurons that project to the brain, the function of this neuronal circuit is unclear. Here, we created a novel mouse allele that inserts a fluorescent reporter at the C1ql1 locus which revealed gene expression in the outer hair cells and allowed creation of outer hair cell-specific C1ql1 knockout mice. We found that C1ql1 expression in outer hair cells corresponds to areas with the most sensitive frequencies of the mouse audiogram, and that it has an unexpected adolescence-onset developmental timing. No expression was observed in the inner hair cells. Since C1QL1 in the brain is made by neurons, transported anterogradely in axons, and functions in the synaptic cleft, C1QL1 may serve a similar function at the outer hair cell afferent synapse. Histological analyses revealed that C1ql1 conditional knockout cochleae may have reduced outer hair cell afferent synapse maintenance. However, auditory behavioral and physiological assays did not reveal a compelling phenotype. Nonetheless, this study identifies a potentially useful gene expressed in the cochlea and opens the door for future studies aimed at elucidating the function of C1QL1 and the function of the outer hair cell and its afferent neurons.
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