Marcus Müller

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

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 x 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.

Frequency representation in the rat cochlea

In order to determine the place-frequency map of the rat cochlea, iontophoretic HRP-injections were made into the cochlear nucleus at electrophysiologically characterized positions. Distribution of retrograde HRP transport in cochlear spiral ganglion cells was analysed by means of a three dimensional reconstruction of the cochlea. The map was established for frequencies between 1.2 and 54 kHz, corresponding to positions between 96.5 to 2% of basilar membrane length (base = 0%). At apex of the cochlea the slope of the place-frequency map was below 0.25 mm/octave. The slope increased to a value of 2.1 mm/octave at 34% basilar membrane length, and remained almost constant towards the cochlear base. The close relationship between frequency range of highest sensitivity and maximum receptor- and innervation-density in the rat cochlea is discussed.

Auditory nerve fibre responses to salicylate revisited

Ototoxicity of salicylate is accompanied by a temporary hearing loss and tinnitus and has therefore been used to study tinnitus in animal models. Salicylate induced elevated central auditory activity has been interpreted as a correlate of tinnitus. Whether this elevated activity in the central auditory system is due to an increased activity in the auditory nerve is still under discussion. To explore this issue, we recorded the activity of single auditory nerve fibres in anaesthetised gerbils following systemic injection of salicylic acid. Firstly, compound action potential (CAP) thresholds were determined at 5-0 min intervals. Fifteen to 30 min after 200 mg/kg salicylic acid, threshold loss developed in the high frequency range. At 2 h CAP threshold loss reached a plateau amounting to 15-20 dB above 16 kHz, 0-5 dB below 2 kHz. An almost immediate start of threshold loss was observed after 400 mg/kg salicylic acid. A plateau of threshold loss was reached after 1.5 h with values of 25 dB in the high, 5-10 dB in the low frequency range. Secondly, responses of single auditory nerve fibres were studied after administration of 200 mg/kg salicylic acid. Frequency tuning curves and rate intensity (RI) functions at characteristic frequency (CF) were measured. Two hours and more after application, single fibre thresholds were elevated by about 20 dB at all CFs. Sharpness of tuning was reduced. Mean spontaneous rate was significantly reduced at CFs below 5 kHz (mean: 44 vs 28 AP/s). At CFs above 5 kHz mean spontaneous rate remained unchanged. In RI functions no change in maximum discharge rate was observed. The altered response properties can be interpreted by the known effects of salicylate on the prestin mediated active process of the outer hair cells. The elevated activity in the central auditory system after salicylate intoxication thus cannot be caused by cochlear nerve hyperactivity.

Inner ear structure electrophysiological audiograms of the subterranean mole rat, Spalax ehrenbergi

Subterranean mole rats of the Spalax ehrenbergi superspecies in Israel have a distinctly developed vocal repertoire, presumably compensating together with olfaction for their complete blindness, thus providing an efficient communication system underground. Here we describe the unique organization of the cochlea of Spalax among mammals. The cochlea is subdivided into different subsystems where in the apical subsystem the fluid space and the organ of Corti differ remarkably from that in the basal subsystem, a feature as yet unknown in other mammals. The audiograms based on cochlear microphonics and on evoked potential recordings from the midbrain and brainstem, reveal a hearing range from 0.1 kHz-10 kHz with a best sensitivity between 0.5 and 1 kHz.

Developmental changes of frequency representation in the rat cochlea

The place-frequency map of the developing rat cochlea was measured by iontophoretic HRP-injections into the ventral cochlear nucleus at electrophysiologically characterized positions. Distribution of retrograde HRP transport in cochlear spiral ganglion cells was analysed by means of a three dimensional reconstruction of the cochlea. Cochlear place-frequency maps were derived in rats of two ages groups: 13 to 22 days, and 36/37 day old animals. These maps were compared with the place-frequency map of adult rats (Müller, 1991). No systematic difference in the place-frequency map between 36/37 day old and adult rats was observed. In animals of the younger age group the place-frequency map (for frequencies above 4 kHz) was shifted towards lower frequencies for a given place along the basilar membrane. The morphological and physiological basis for this frequency shift during development is discussed.

Structure and function of the cochlea in the African mole rat (Cryptomys hottentotus): evidence for a low frequency acoustic fovea

SummaryThe cochlea of the mole rat Cryptomys hottentotus was investigated with physiological and anatomical methods. In order to reveal the place-frequency map of the cochlea, iontophoretic HRP-applications were made in the cochlear nucleus at physiologically characterized locations. Subsequent HRP-transport in auditory nerve fibres and labeling patterns of spiral ganglion cells within the cochlea were evaluated.A cochlear place-frequency map was constructed from 17 HRP-applications in the cochlear nucleus at positions where neurons had characteristic frequencies between 0.1 and 12.6 kHz. As in other mammals, high frequencies were found to be represented at the cochlear base, low frequencies at the cochlear apex. The placefrequency map had three distinct parts which were characterized by their different slopes. A clear overrepresentation of the frequencies between 0.6 and 1 kHz was revealed, in this frequency range the slope of the place-frequency map amounted to 5.3 mm/octave. As calculated from the regression analysis, below 0.6 kHz the slope of the cochlear place-frequency map amounted to 0.24 mm/octave, above 1 kHz to 0.9 mm/octave.As in other mammals width of the basilar membrane (BM) increased from the cochlear base towards the cochlear apex. Also in concordance with the findings in other mammals, BM-thickness decreased from the cochlear base to the apex. However, it was remarkable to find that there was no or little change in BM-width and thickness between 40 and 85% BM-length. It was also revealed that scala tympani was only 1/10th the size found in the rat or other mammals of similar body size.On the basis of the cochlear place-frequency map and the morphological findings we speculate that in Cryptomys hottentotus an acoustic fovea is present in the frequency range between 0.6 and 1 kHz. In analogy to echolocating bats, about half of the cochlea is devoted to the analysis of a narrow frequency band within the hearing range.

Cochlear place-frequency map in the marsupial Monodelphis domestica

In order to determine the place-frequency map of the cochlea in the marsupial Monodelphis domestica, iontophoretic HRP-injections were made at several locations in the ventral cochlear nucleus. Prior to iontophoresis the auditory neurons at these locations were characterized electrophysiologically. The resulting distribution of retrogradely labeled cochlear spiral ganglion cells was analysed by means of a three dimensional reconstruction of the cochlea. The map was established for frequencies between 2.4 and 44.5 kHz, corresponding to positions between 95 to 14% of basilar membrane length (base = 0%). The maximum slope amounted to 1.8 mm/octave. Over the basal-most 60% of the cochlea the slope of the place-frequency map was larger than 1.5 mm/octave, further apically the slope rapidly decreased to values below 0.8 mm/octave. The shape of the cochlear place-frequency map is similar to that described in placental mammals.

ACOUSTIC DISTORTION PRODUCTS FROM THE COCHLEA OF THE BLIND AFRICAN MOLE RAT, CRYPTOMYS SPEC.

The measurement of distortion-product otoacoustic emissions is a noninvasive method that can be used for assessing the sensitivity and the frequency tuning of nonlinear cochlear mechanics. During stimulation with two pure tones f1 and f2, the acoustic 2f1-f2 distortion was recorded in the ear canal of Cryptomys spec. to study specializations in cochlear mechanics that could be associated with the presence of a frequency expanded cochlear region between 0.8–1 kHz. In addition, a distortion threshold curve was obtained which describes relative threshold of nonlinear cochlear mechanics. Sensitive distortion thresholds could be measured for stimulus frequencies between 0.4 to 18 kHz with a broad minimum between 0.75 to 2.5 kHz. The distortion threshold curve extends to higher frequencies than previous neuronal data indicated.As a measure of mechanical tuning sharpness in the cochlea, suppression tuning curves of 2f1-f2 were recorded. The tuning curves reflected the typical mammalian pattern with shallow low frequency and steep high frequency slopes. Their tuning sharpness was poor with Q10dB values between 0.3 and 1.88. In the range of the frequency expanded region, the Q10dB values were below 0.5. This finding emphasizes that the presence of frequency expansion does not necessarily lead to enhanced mechanical tuning in the cochlea and one has to consider if in certain bat species with cochlear frequency expansion and particularly sharp cochlear tuning, the two phenomena may not be interlinked.

Preferred intervals in birds and mammals: A filter response to noise?

Quasi-periodic spontaneous activity (preferred intervals, PIs) has been reported from avian primary auditory afferents. In mammals, PIs have not been reported, as yet. As the length of PIs is close to 1/characteristic frequency, it has been suggested that this type of spontaneous activity indicates particular mechanisms in avian inner ear transduction. However, the present paper shows that pigeon auditory fibres possessing preferred intervals in their spontaneous activity always belong to the most sensitive and the most sharply-tuned fibres recorded. This leads to the assumption that preferred intervals are the response of narrow-band filters to noise. This view is supported by three additional findings: (i) Near-threshold noise provokes PIs in avian fibres that show no spontaneous PIs. (ii) Similarly, PIs can also be evoked in mammalian (gerbil) auditory afferents by low level noise. (iii) Phase-locking of auditory afferents can be achieved by sound stimuli 10-20 dB below rate threshold. It is argued that no conclusions may be drawn from the presence of PIs about the nature of the underlying filter.

Shift in the cochlear place-frequency map after noise damage in the mouse.

The cochlear place-frequency map, determined from noise-damaged mice, is shifted to lower frequencies by up to one octave compared with the map determined from normal hearing mice. To test the hypothesis that the shift results from damage to the cochlear amplifier, we measured frequency tuning curves from the same neurons before and after noise exposure. Noise damage resulted in loss of tuning and elevation of thresholds. The neuronal characteristic frequency shifted by 0.6–1.2 octaves, dependent on frequency. The shift in characteristic frequency was used to calculate a shifted place–frequency map. We conclude that desensitization of areas in the inner ear after noise exposure can explain the shift of the map after noise damage relative to the normal physiological map.