Nigel K. Woolf

The development of auditory function in the cochlea of the mongolian gerbil.

Cochlear microphonic (CM) potentials were recorded throughout the development of auditory function in the Mongolian gerbil. CM responses were first recorded at 12 days after birth (DAB), with thresholds exceeding 103 dB SPL. CM thresholds subsequently improved rapidly in a parallel fashion across the responsive frequency range, achieving adult levels by 18 DAB. There was no evidence from CM thresholds of a preferential rate of maturation for either the high or low frequency ranges. CM responses to suptrathreshold stimulation were also studied throughout development. At all responsive ages, CM input-output functions increased logarithmically to a saturating maximum value and then declined. Maximum CM responses increased continuously throughout development in a parallel fashion across all frequencies. The dynamic range of the CM input-output functions (the intensity interval from CM threshold to maximum CM value) also developed in a parallel manner across frequencies, but reached mature assymptotic values by 16 DAB. The results suggest that throughout the adult CM frequency range cochlear hair cell function develops simultaneously.

Neural phase-locking properties in the absence of cochlear outer hair cells.

A combined regimen of kanamycin sulfate treatment (175 mg/kg/day) and behavioral evaluation of resulting audiometric threshold shifts was used to produce selective outer hair cells (OHC) loss in chinchillas. This protocol resulted in a 3-7 mm region in the cochlear base in which OHCs were completely absent and inner hair cells (IHCs) were largely resent and normal at both light and electron microscopic levels. Partial OHC loss was associated with audiometric threshold shifts in excess of 15 dB, while complete OHC loss was associated with audiometric threshold shifts in excess of 40 dB. After recovery periods of at least three weeks, phase-locking was examined across frequency for auditory nerve (VIIIth nerve) and ventral cochlear nucleus (VCN) neurons. The frequency range for neural phase-locking in normal subjects extended up to approximately 4 kHz for VIIIth nerve fibers and 3 kHz for VCN neurons. Following kanamycin intoxication, however, the frequency range for neural phase-locking in both of these auditory regions varied with characteristic frequency (CF): neurons whose CF corresponded to normal cochlear regions exhibited phase-locking throughout the normal frequency range; neurons whole CF corresponded to cochlear regions with selective OHC loss exhibited a marked reduction in the frequency range over which they could phase-lock.

The spatial representation of frequency in the rat dorsal cochlear nucleus and inferior colliculus

The spatial distribution of neural activity produced by tones was assessed in the rat dorsal cochlear nucleus (DCN) and inferior colliculus (IC), using the 2-deoxyglucose (2-DG) technique. Eight pure tones, spanning the range of reported single unit characteristic frequencies in the rat, were presented at 40 dB above behavioral threshold. The relationship between frequency of stimulation and location of neural activity within each nucleus was evaluated quantitatively. Based on the 2-DG uptake pattern across animals, a tonotopic axis in the transverse plane was defined for each nucleus. This axis transected the centers of regions of evoked 2-DG uptake for each frequency. There was an orderly relationship between stimulus frequency and the location of evoked neural activity along the axis. Each pure tone stimulus activated an approximately equal proportion of this axis, for all frequencies tested, in both the DCN and IC. This suggests the existence of equal spatial bandwidths, in rat central auditory structures, across its entire frequency range. Equal spatial bandwidths could facilitate signal analysis strategies which require interaction between neurons with closely-related CFs. In the horizontal plane, however, the proportion of stimulated tissue was not equal across frequency. High-frequency (greater than 8 kHz) tones produced increased neural activity along a much greater extent of the anterior-to-posterior axis of the IC than did low-frequency tones.(ABSTRACT TRUNCATED AT 250 WORDS)

Functional ontogeny in the central auditory pathway of the mongolian gerbil - A 2-deoxyglucose study

SummaryThe 2-deoxyglucose (2-DG) autoradiographic technique was used to map functional activity in the central auditory system of the mongolian gerbil, throughout the period of functional onset. Uptake of 2-DG during exposure to 105 dB SPL wide band noise (WBN) was compared to silence in adults and in neonates at 12, 14, 16 and 18 days after birth (DAB). At 12 DAB, WBN exposure increased 2-DG uptake relative to silence only in the ventral cochlear nucleus. At 14 DAB, 2-DG uptake increased during WBN in the entire cochlear nuclear complex, superior olivary complex, and ventral nucleus of the lateral lemniscus. These stimulus-evoked increases in 2-DG uptake were at adult levels. However, little or no stimulus-evoked increase was seen in higher auditory nuclei at 14 DAB. By 16 DAB, 2-DG uptake also increased during WBN exposure in the dorsal nucleus of the lateral lemniscus, inferior colliculus and medial geniculate nucleus. By 18 DAB, WBN exposure produced increases in 2-DG uptake of medullary and pontine auditory nuclei which exceeded those seen in adults. At higher levels of the pathway, increases were comparable to those seen in adults. WBN-induced increases in 2-DG uptake observed in the cochlear nuclear and superior olivary complexes of neonates were comparable in all regions at all ages, even at 12 DAB. However, the 2-DG uptake increases observed at 16 and 18 DAB were appreciably greater in those regions of the inferior colliculus and medial geniculate nucleus which respond to high frequencies.

Development of tonotopic representation in the Mongolian gerbil: a 2-deoxyglucose study

The spatial representation of frequency in the central auditory system of the neonatal gerbil was mapped with the 2-deoxyglucose (2-DG) autoradiographic technique. At 14 days after birth (DAB), pure tone stimulation produced recognizable patterns of 2-DG uptake. However, at this age, tone-induced areas of increased 2-DG uptake occurred at locations which in the adult respond to higher frequencies. The degree of shift in tonotopic representation was approximately two octaves. The normal adult tonotopic organization of auditory nuclei was achieved by 18 DAB, consistent with the rapid development of auditory function in the gerbil. The results suggest that the spatial distribution of frequency in the cochlea of neonatal animals is different from that in adults. Stimulus-evoked 2-DG uptake occurred first in brainstem auditory nuclei, and was observed in midbrain and forebrain auditory structures only at later ages. This is consistent with a sequential development of function in the central auditory pathway.

Protection from noise-induced hearing loss by prior exposure to a nontraumatic stimulus: role of the middle ear muscles.

Recent evidence suggests that prior exposure to a moderate-level acoustic stimulus can reduce damage due to later exposure to the same stimulus at high intensity [Canlon et al., Hear. Res. 34, 197-200 (1988)]. To test the role of the middle ear muscles (MEMs) in this phenomenon, Mongolian gerbils were conditioned by exposure to a two-octave band of noise (1414-5656 Hz) at 81 dB SPL for 3 weeks. Either immediately afterward, or following a one week rest period, they were exposed to the same stimulus at 110 dB SPL for one hour. The ABR thresholds of these animals were compared to those seen in animals exposed at 110 dB SPL without conditioning. The MEMs of one ear in each subject were cut, to determine their role in any noise trauma protection effects. In the unoperated ears, conditioning without a recovery period did not alter the effects of the 110 dB stimulus. Conditioning followed by a one week recovery period reduced both temporary (TTS) and permanent (PTS) threshold shift. MEM section had no effect on either TTS or PTS in unconditioned subjects, and did not alter the reduction in TTS or PTS seen with conditioning. It is concluded that the noise trauma resistance provided by acoustic conditioning is not mediated by the MEMs.

Increasing intensities of wide band noise increase [14C]2-deoxyglucose uptake in gerbil central auditory structures

The [14C]2-deoxyglucose (2DG) technique has been used to map the effects of increasing intensities of wide band noise on 2DG uptake in mongolian gerbil brain auditory structures. Animals were injected with [14C]2DG and exposed to silence or continuous wide band noise at 25 dB, 45 dB, 65 dB, 85 dB or 105 dB SPL. Brains were removed, frozen-sectioned and autoradiographed on X-ray film. The ratio of the optical density of gray matter structures to the optical density of cerebellar peduncles in each animal was used to semiquantitate the results. The dorsal and ventral cochlear nuclei, superior olive/trapezoid body, inferior colliculus, and the dorsal and ventral nuclei of the lateral lemniscus all showed increases in 2DG uptake during exposure to wide band noise (WBN). As noise intensity increased from 0 to 105 dB SPL, 2DG uptake increased regularly to a maximum at 85 or 105 dB SPL. As WBN intensity increased, deeper layers of inferior colliculus were activated. The medial geniculate nucleus and auditory cortex showed a lesser increase in 2DG uptake during noise exposure. Non-auditory structures, including the cerebellar cortex and the medullary reticular nuclei, showed no increase in 2DG uptake during noise exposure at any intensity tested.

A Reexamination of Experimental Type II Collagen Autoimmunity: Middle and Inner Ear Morphology and Function

Type II collagen autoimmunity has been reported to result in a number of middle and inner ear morphological and functional abnormalities. We investigated the immunological, electrophysiological, and anatomical effects of this autoimmune state in well-established Wistar-Furth rat models of type II collagen autoimmune arthritis. Seventeen animals immunized with bovine type II collagen were divided into short term (1–3 months postimmunization) and long term (9–11 months) groups. Thirty-three experimental ears were tested electrophysiologically and were compared to nine ears of unimmunized Wistar-Furth rats. No hearing loss was found in the immunized animals, except for four animals that showed middle ear abscess formation consistent with spontaneous, purulent otitis media. All immunized animals showed very significant serum and perilymph antibody titers to type II collagen. No morphological abnormalities of the external, middle, or inner ears could be identified in the noninfected experimental animals. These findings do not support previously reported observations that type II collagen autoimmunity results in ear disease.

Cochlear Pathophysiology Associated with Inner Ear Immune Responses

The effects of primary and secondary inner ear immune responses were investigated in the guinea pig. Subjects were immunized with keyhole limpet hemocyanin (KLH). Serum and perilymph anti-KLH titers, cochlear microphonic (CM) and VIII nerve N1 compound action potential (AP) thresholds, and cochlear morphology were examined at 2 or 4 weeks post-inner ear KLH inoculation. Primary inner ear immunized subjects developed serum and perilymph anti-KLH titers, exhibited minimal cochlear histopathology and showed only small changes in CM and AP thresholds at 2 or 4 weeks post-inner ear inoculation. Secondary immune response animals, those which were systemically immunized with KLH prior to inner ear challenge, showed significant serum and perilymph anti-KLH titers, and normal CM and AP thresholds at the time of inner ear challenge. At 2 or 4 weeks following inner ear challenge, secondary immunized animals showed very significant increases in CM and AP thresholds, and marked cochlear histopathology. We conclude that secondary inner ear challenge results in significant cochlear pathophysiology, while primary inner ear immunization does not.

Auditory stimulation alters the pattern of 2-deoxyglucose uptake in the inner ear

The 2-deoxy-D-glucose (2-DG) autoradiographic technique was adapted for application to the inner ear. The uptake of [14C]-DG during silence was compared with that observed during exposure to wide band noise (WBN) or pure tones at an intensity level of 85 db SPL. In silence, the highest levels of 2-DG uptake were observed in the spiral ligament, spiral prominence and stria vascularis, with approximately equal levels of uptake in each structure. The high levels of 2-DG uptake observed in the ligament and prominence are surprising, and suggest a more active role for these structures in cochlear function than has previously been suspected. Levels of uptake in the organ of Corti, spiral ganglion and VIIIth nerve were much lower, although well above background. During exposure to WBN, 2-DG uptake increased markedly in the VIIIth nerve, and spiral ganglion throughout the cochlea, and in the organ of Corti in the lower basal turn. 2-DG uptake did not change significantly in the spiral ligament or stria vascularis. During pure tone exposure, increased 2-DG uptake was noted in localized regions of the VIIIth nerve and spiral ganglion.