Research note

Acoustic trauma-induced developmental change in the acoustic startle response and audiogenic seizures in mice

In recent years, there has been increasing use of the gap detection reflex test to demonstrate induction of tinnitus in animals. Animals with tinnitus show weakened gap detection ability for background noise that matches the pitch of the tinnitus. The usual explanation is that the tinnitus ‘fills in the gap’. It has recently been shown, however, that tinnitus is commonly associated with hyperacusis-like enhancements of the acoustic startle response, a change which might potentially alter responses in the gap detection test. We hypothesized that such enhancements could lead to an apparent reduction of gap suppression, resembling that caused by tinnitus, by altering responses to the startle stimulus or the background noise. To test this hypothesis, we compared gap detection abilities in 3 subsets of noise-exposed animals with those in unexposed controls. The results showed that exposed animals demonstrated altered gap detection abilities, but these alterations were sometimes explained as consequences of hyper-responsiveness to either the startle stimulus or to the background noise. Two of the three subsets of animals studied, however, displayed weakened gap detection abilities that could not be explained by enhanced responses to these stimuli or by reduced sound sensitivity or a reduction of temporal processing speed, consistent with the induction of tinnitus. These results demonstrate that not only hearing loss but also changes in sensitivity to background noise or to startle stimuli are potential confounds that, when present, can underlie changes in gap detection irrespective of tinnitus. We discuss how such confounds can be recognized and how they can be avoided.

Even brief acoustic trauma during the critical period of development that results in no permanent hearing threshold shift may lead to altered auditory processing in adulthood. By monitoring the acoustic startle response (ASR), we examined the development of auditory function in control rats and in rats exposed to intense noise at the 14th postnatal day (P14). First ASRs appeared on P10–P11 to intense low-frequency tones. By P14, the range of sound intensities and frequencies eliciting ASRs extended considerably, the ASR reactivity being similar at all frequencies (4–32 kHz). During the subsequent two weeks, ASR amplitudes to low-frequency stimuli (4–8 kHz) increased, whereas the ASRs to high-frequency tones were maintained (16 kHz) or even decreased (32 kHz). Compared to controls, noise exposure on P14 (125 dB SPL for 8, 12, or 25 min) produced transient hyper-reactivity to startle stimuli, manifested by a decrease of ASR thresholds and an increase of ASR amplitudes. ASR enhancement occurred regardless of permanent hearing loss and was more pronounced at high frequencies. The hyper-reactivity of ASRs declined by P30; the ASR amplitudes in adult exposed rats were lower than in controls. The histological control did not reveal loss of hair cells in adult exposed rats, however, the number of inner hair cell ribbon synapses was significantly decreased, especially in the high-frequency part of the cochlea. The results indicate that early acoustic trauma may result in complex changes of ASRs during development.

Loudness is the primary perceptual correlate of sound intensity. The relationship between sound intensity and loudness is not fixed, and can be modified by short-term sound deprivation or stimulation. Deprivation increases sound sensitivity, whereas stimulation decreases it. We review the effects of short-term auditory deprivation and stimulation on the auditory central nervous system of humans and animals, and we extend the discussion to permanent auditory deprivation (hearing loss) and auditory pathologies of loudness perception. Although there is sufficient evidence to conclude that loudness can be modulated in normal hearing listeners by temporary sound deprivation and stimulation, evidence is scanter for the hearing-impaired listeners. In addition, cortical effects of sound deprivation and stimulation in humans, which may correlate with loudness coding, are still largely unknown and should be the target of future research.

Recent clinical reports found a high incidence of recurrent otitis media in children suffering hyperacusis, a marked intolerance to an otherwise ordinary environmental sound. However, it is unclear whether the conductive hearing loss caused by otitis media in early age will affect sound tolerance later in life. Thus, we have tested the effects of tympanic membrane (TM) damage at an early age on sound perception development in rats. Two weeks after the TM perforation, more than 80% of the rats showed audiogenic seizure (AGS) when exposed to loud sound (120 dB SPL white noise, < 1 min). The susceptibility of AGS lasted at least sixteen weeks after the TM damage, even the hearing loss recovered. The TM damaged rats also showed significantly enhanced acoustic startle responses compared to the rats without TM damage. These results suggest that early age conductive hearing loss may cause an impaired sound tolerance during development. In addition, the AGS can be suppressed by the treatment of vigabatrin, acute injections (250 mg/kg) or oral intakes (60 mg/kg/day for 7 days), an antiepileptic drug that inhibits the catabolism of GABA. c-Fos staining showed a strong staining in the inferior colliculus (IC) in the TM damaged rats, not in the control rats, after exposed to loud sound, indicating a hyper-excitability in the IC during AGS. These results indicate that early age conductive hearing loss can impair sound tolerance by reducing GABA inhibition in the IC, which may be related to hyperacusis seen in children with otitis media.

Noise exposure during the critical period of postnatal development in rats results in anomalous processing of acoustic stimuli in the adult auditory system. In the present study, the behavioral consequences of an acute acoustic trauma in the critical period are assessed in adult rats using the acoustic startle reflex (ASR) and prepulse inhibition (PPI) of ASR. Rat pups (strain Long–Evans) were exposed to broad-band noise of 125 dB SPL for 8 min on postnatal day 14; at the age of 3–5 months, ASR and PPI of ASR were examined and compared with those obtained in age-matched controls. In addition, hearing thresholds were measured in all animals by means of auditory brainstem responses. The results show that although the hearing thresholds in both groups of animals were not different, a reduced strength of the startle reflex was observed in exposed rats compared with controls. The efficacy of PPI in exposed and control rats was also markedly different. In contrast to control rats, in which an increase in prepulse intensity was accompanied by a consistent increase in the efficacy of PPI, the PPI function in the exposed animals was characterized by a steep increase in inhibitory efficacy at low prepulse intensities of 20–30 dB SPL. A further increase of prepulse intensity up to 60–70 dB SPL caused only a small and insignificant change of PPI. Our findings demonstrate that brief noise exposure in rat pups results in altered behavioral responses to sounds in adulthood, indicating anomalies in intensity coding and loudness perception.

Audiogenic seizure (AGS) susceptibility is a reflex epilepsy of rodents in which acoustic stimulation evokes wild running attacks and subsequent convulsions. Susceptibility can be induced in non-susceptible strains by treatments causing transient or permanent hearing losses as long as these occur during the neonatal period. The defect which is the basis of susceptibility has been proposed to be a failure of developmental organization of inferior colliculus (IC) into frequency selective zones. That is, high frequency stimuli evoke responses in broader arrays of neurons in ICs of susceptible rats than in those of neonatally untreated (non-susceptible) controls. Nonetheless, this observation has been made only in rats in which susceptibility was induced by exposure to intense noise on postnatal day (PND) 14. By contrast, the present study examines whether unusually broad topographic responses are also characteristic in ICs of rats made susceptible by the neonatal administration of low doses of the ototoxic antibiotic, kanamycin (KM). Patterns of Fos-like immunoreactivity (Fos_lir) induced by seizures or pure tone stimuli were compared in ICs of adult Wistar rats which neonatally had been (a) sham-treated; (b) noise-exposed on PND 14; or (c) injected on PNDs 9–12 with 100 mg/kg KM. It was found that sound-triggered seizures in the two experimental groups resulted in induction of Fos_lir primarily within cortical areas of IC. By contrast, pure tones evoked unusually broad responses in the central nucleus of ICs of both susceptible groups but not in those of controls. Additionally, in the KM-treated rats, the range of frequencies evoking abnormal responses extended one octave lower than was characteristic of noise-exposed rats. The earlier schedule of treatments in the KM model may account for this inasmuch as low frequency response domains undergo development at younger ages. The similarity of results in the two models suggests failure of development of frequency selective fields in IC is indeed the common basis of experimentally induced susceptibility to sound-triggered seizures.