A physiological place–frequency map of the cochlea in the CBA/J mouse

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Abstract

Genetically manipulated mice have gained a prominent role in in vivo research on development and function of the auditory system. A prerequisite for the interpretation of normal and abnormal structural and functional features of the inner ear is the exact knowledge of the cochlear place–frequency map. Using a stereotaxic approach to the projection site of the auditory nerve fibers in the cochlear nucleus, we succeeded in labelling physiologically characterized auditory nerve afferents and determined their peripheral innervation site in the cochlea.

From the neuronal characteristic frequency (CF) and the innervation site in the organ of Corti a place–frequency map was established for characteristic frequencies between 7.2 and 61.8 kHz, corresponding to locations between 90% and 10% basilar membrane length (base = 0%, apex = 100%, mean length measured under the inner hair cells 5.13 mm). The relation between normalized distance from the base (d) and frequency (kHz) can be described by a simple logarithmic function: d(%) = 156.5  82.5 × log(f), with a slope of 1.25 mm/octave of frequency. The present map, recorded under physiological conditions, differs from earlier maps determined with different methods. The simple logarithmic place–frequency relation found in the mouse indicates that mice are acoustic generalists rather than specialists.

Introduction

Mice have gained a prominent role in auditory research because of the enormous possibilities opened by new methods in molecular biology and genetic engineering. Transgenic and gene targeting technologies in mice allow in vivo analysis of the functional role of specific genes. Genetically modified mice therefore have become a major source in acquiring more insights into the development and function of the auditory system. However, since the inner ear in mice is very small and difficult to handle when compared to cat or guinea pig, only limited information is available concerning basic physiologic parameters of the peripheral auditory system. One very important parameter is the projection of frequency along the cochlear partition, the cochlear place–frequency map, obtained under normal physiological conditions. The exact knowledge of the cochlear place–frequency map under such conditions is a prerequisite for the interpretation of normal and abnormal structural and functional features of the inner ear. Normal physiological conditions require an untouched cochlea, and when acoustic stimuli are applied for its determination they must not reach sound pressure levels that could damage the cochlea. A physiological place–frequency map can therefore only be established by labelling physiologically characterized auditory nerve fibers in vivo and tracing their peripheral course to the innervation site in the cochlea histologically. Such maps have been established in a number of species (cat: Liberman, 1982; mustache bat: Kössl and Vater, 1985; fat tailed gerbil: Müller, 1990; Müller et al., 1991a; rat: Müller, 1991a, Müller, 1991b; mole rat: Müller et al., 1992; opossum: Müller et al., 1993; Mongolian gerbil: Müller, 1996), but not in the mouse. The small size of the mouse auditory periphery makes physiological recordings from the auditory nerve very difficult. Using a stereotaxic approach to the projection site of the auditory nerve fibers in the cochlear nucleus, we succeeded in labelling physiologically characterized auditory nerve afferents and determined a physiological place–frequency map in the normal mouse cochlea.

Estimates of the cochlear place–frequency maps of mice explored with different methods are available, however, none of them satisfy the above-mentioned physiological conditions. Based on direct observations of the travelling wave in cochlear explants, Georg von Békésy (1944) determined the first place–frequency map of the mouse post-mortem. However, it has been shown in a number of species, for example in rat (Müller, 1991b), that the place–frequency map post-mortem deviates by 1–2 octaves from that determined under physiological conditions. Based on behavioral experiments, Ehret (1975) presented a map of the mouse cochlea. There are however theoretical assumptions in the construction of this map, which still have to be experimentally proven. Recently Ou et al. (2000) determined an anatomically based place–frequency map. After noise exposure the latter authors correlated histological lesions of cochlear hair cells with permanent threshold shifts obtained from auditory brainstem response (ABR) measurements. Inherent to this method, however, is the use of sound exposure levels that destroy the hair cells in the cochlea leading to abnormal cochlear function.

The most accurate way to obtain cochlear place–frequency maps is the injection of a tracer into single physiologically characterized auditory nerve fibers in vivo. However, in small mammals like the mouse, the cochlear nerve is very hard to access, especially when the experiment requires considerable survival time of the animal, as is the case in tracing experiments. We therefore used the method introduced in the horseshoe bat (Vater et al., 1985), injecting a neuronal tracer (HRP) into the cochlear nucleus at physiologically characterized sites in vivo. Subsequently the retrograde transport pattern of HRP into the cochlea was analysed. The physiological place–frequency map of the mouse inner ear determined this way, shows a simple linear relation of location along the cochlear partition as a function of log(frequency).

Section snippets

Animals

Experiments were performed on CBA/J mice (Mus musculus) of either sex aged 6–13 weeks (average 7.7 weeks). The total number of animals used in this study amounted to 79. Animals were obtained from Charles River and kept in our animal housing. First and second generation offspring of these animals were also used. The care and use of the animals reported in this study was approved by the state authorities responsible (Regierungspräsidium Darmstadt).

Stimulation and recording

Electrophysiological recordings were performed

ABRs

The mean ABR-threshold of 39 normal hearing animals is shown in Fig. 2. Mice had a mean ABR-audiogram with best thresholds of 36 dB SPL at 11.3 and 16 kHz. Above and below that frequency mean thresholds rose to 81 dB SPL at 2 kHz and 70 dB SPL at 45 kHz.

Single-unit responses

A total of 178 tuning curves were recorded from 73 animals. CFs of the recorded neurons ranged from 4.07 to 75.11 kHz. Thresholds at CF of the neurons are shown in Fig. 3. Neurons are divided into two samples, one emanating from animals where

Response properties

The CF-range and threshold at CF of the auditory nerve fibers and/or cochlear nucleus neurons of CBA/J mice, reported in the present study, were similar to those reported by Ehret and Moffat (1984) in NMRI mice and Taberner and Liberman (2003) in CBA/CaJ mice. Also there was no difference in CF-thresholds of mice injected successfully with HRP and those in which the injection site could not be verified. Together with the normal ABR-threshold curves which remained unchanged during the

Acknowledgments

We thank George Ezeani for technical assistance. The study was supported by the Deutsche Forschungsgemeinschaft, SFB 269, B1.

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