Zbyněk Bureš

Brief exposure of juvenile rats to noise impairs the development of the response properties of inferior colliculus neurons

Temporary impairment of the auditory periphery during the sensitive period of postnatal development of rats may result in a deterioration of neuronal responsiveness in the central auditory nuclei of adult animals. In this study, juvenile rats (postnatal day 14) were exposed for 8 min to intense broad‐band noise; at the age of 3–6 months, the excitatory and inhibitory response areas of neurons in the central nucleus of the inferior colliculus were recorded under ketamine–xylazine anaesthesia in these animals and compared with those of age‐matched controls. The response thresholds were similar in the exposed and control animals. The frequency selectivity of low‐frequency neurons was comparable in both groups; however, high‐frequency neurons had significantly wider excitatory response areas in the exposed rats, indicating disrupted development of high‐frequency hearing. Forty‐one per cent and 25% of neurons in exposed animals and in controls, respectively, lacked a distinct inhibitory area; these neurons had similar frequency selectivity in the exposed and control rats. As the presence of an inhibitory sideband was associated with sharper frequency tuning in both groups, it appears that lateral inhibition substantially influences neuronal frequency selectivity. If present, the inhibitory areas had comparable bandwidths in both groups; however, they were shifted to the side in the exposed animals, allowing the expansion of the excitatory areas. The results indicate that a brief exposure of juvenile rats to noise leads to a significant worsening of the frequency selectivity of inferior colliculus neurons in adult animals; the poorer frequency selectivity may be due to missing or displaced inhibitory sidebands.

Noise exposure during early development impairs the processing of sound intensity in adult rats

During the early postnatal development of rats, the structural and functional maturation of the central auditory nuclei strongly relies on the natural character of the incoming neural activity. Even a temporary deprivation in the critical period results in a deterioration of neuronal responsiveness in adult animals. We demonstrate that besides the poorer frequency selectivity of neurons in the impaired animals reported previously [ Grecova et al. (2009)Eur. J. Neurosci. 29, 1921–1930], the neuronal representation of sound intensity is significantly affected. Rate–intensity functions of inferior colliculus neurons were recorded in anaesthetized adult rats that were exposed to intense noise at postnatal day 14, and compared with those obtained in age‐matched controls. Although the response thresholds were similar in the exposed and control rats, the neurons in the exposed animals had a longer first‐spike latency, a narrower dynamic range, lower maximum response magnitudes and a steeper slope of the rate–intensity functions. The percentage of monotonic neurons was significantly lower in the exposed animals. The observed anomalies were confined to the mid‐ and high‐frequency regions, whereas no significant changes were found in the low‐frequency neurons. The altered parameters of the individual rate–intensity functions led also to differences in the cumulative responses. We conclude that a brief noise exposure during the critical period leads to a frequency‐dependent alteration of the sound intensity representation in the inferior colliculus of adult rats. The results suggest that such impairments may appear in individuals with normal hearing thresholds, but with a history of noise exposure very early in childhood.

Noise exposure during early development influences the acoustic startle reflex in adult rats

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.

Development of the acoustic startle response in rats and its change after early acoustic trauma.

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.

Acoustical enrichment during early postnatal development changes response properties of inferior colliculus neurons in rats.

The structure and function of the auditory system may be influenced by acoustic stimulation, especially during the early postnatal period. This study explores the effects of an acoustically enriched environment applied during the third and fourth week of life on the responsiveness of inferior colliculus neurons in rats. The enrichment comprised a spectrally and temporally modulated complex sound reinforced with several target acoustic stimuli, one of which triggered a reward release. The exposure permanently influenced neuronal representation of the sound frequency and intensity, resulting in lower excitatory thresholds at neuronal characteristic frequency, an increased frequency selectivity, larger response magnitudes, steeper rate–intensity functions and an increased spontaneous activity. The effect was general and non‐specific, spanning the entire hearing range – no changes specific to the frequency band of the target stimuli were found. The alterations depended on the activity of animals during the enrichment – a higher activity of rats in the stimulus–reward paradigm led to more profound changes compared with the treatment when the stimulus–reward paradigm was not used. Furthermore, the exposure in early life led to permanent changes in response parameters, whereas the application of the same environment in adulthood influenced only a subset of the examined parameters and had only a temporary effect. These findings indicate that a rich and stimulating acoustic environment during early development, particularly when reinforced by positive feedback, may permanently affect signal processing in the subcortical auditory nuclei, including the excitatory thresholds of neurons and their frequency and intensity resolution.

Age-related changes in the acoustic startle reflex in Fischer 344 and Long Evans rats.

The behavioral consequences of age-related changes in the auditory system were studied in Fischer 344 (F344) rats as a model of fast aging and in Long Evans (LE) rats as a model of normal aging. Hearing thresholds, the strength of the acoustic startle responses (ASRs) to noise and tonal stimuli, and the efficiency of the prepulse inhibition (PPI) of ASR were assessed in young-adult, middle-aged, and aged rats of both strains. Compared with LE rats, F344 rats showed larger age-related hearing threshold shifts, and the amplitudes of their startle responses were mostly lower. Both rat strains demonstrated a significant decrease of startle reactivity during aging. For tonal stimuli, this decrease occurred at an earlier age in the F344 rats: middle-aged F344 animals expressed similar startle reactivity as aged F344 animals, whereas middle-aged LE animals had similar startle reactivity as young-adult LE animals. For noise stimuli, on the other hand, a similar progression of age-related ASR changes was found in both strains. No significant relationship between the hearing thresholds and the ASR amplitudes was found within any age group. Auditory PPI was less efficient in F344 rats than in LE rats. An age-related reduction of the PPI of ASR was observed in rats of both strains; however, a significant reduction of PPI occurred only in aged rats. The results indicate that the ASR may serve as an indicator of central presbycusis.

The Effect of Complex Acoustic Environment during Early Development on the Responses of Auditory Cortex Neurons in Rats

Acoustical environment plays an important role during the maturation of the auditory system. It has been shown that the sensory inputs to the developing centres influence the development of the structure of projections, neuronal responsiveness, excitatory-inhibitory balance, or tonotopical arrangement, throughout the auditory pathway. Our previous study (Bures et al., 2014) showed that rats reared in a complex acoustic environment (spectrally and temporally modulated sound reinforced by an active behavioural paradigm with a positive feedback) exhibit permanently improved response characteristics of the inferior colliculus (IC) neurons. Extending these results, the current work provides evidence that the changes occur also at the level of auditory cortex (AC). In particular, the enriched animals have lower excitatory thresholds, sharper frequency selectivity, and a lower proportion of non-monotonic rate-intensity functions. In contrast to the changes observed in the IC, the cortical neurons of enriched animals have lower response magnitudes. In addition, the enrichment changed the AC responsiveness to frequency-modulated and also to a lesser extent, amplitude-modulated stimuli. Significantly, the alterations span the entire hearing range and may be regarded as general and not directly linked to the characteristics of the acoustical stimulation. Furthermore, these developmentally induced changes are permanent and detectable in adulthood. The findings indicate that an acoustically enriched environment during the critical period of postnatal development influences basic properties of neuronal receptive fields in the AC, which may have implications for the ability to detect and discriminate sounds.

Auditory dysfunction in patients with Huntington’s disease

OBJECTIVE Huntingtons disease (HD) is an autosomal, dominantly inherited, neurodegenerative disease. The main clinical features are motor impairment, progressive cognitive deterioration and behavioral changes. The aim of our study was to find out whether patients with HD suffer from disorders of the auditory system. METHODS A group of 17 genetically verified patients (11 males, 6 females) with various stages of HD (examined by UHDRS - motor part and total functional capacity, MMSE for cognitive functions) underwent an audiological examination (high frequency pure tone audiometry, otoacoustic emissions, speech audiometry, speech audiometry in babble noise, auditory brainstem responses). Additionally, 5 patients underwent a more extensive audiological examination, focused on central auditory processing. The results were compared with a group of age-matched healthy volunteers. RESULTS Our results show that HD patients have physiologic hearing thresholds, otoacoustic emissions and auditory brainstem responses; however, they display a significant decrease in speech understanding, especially under demanding conditions (speech in noise) compared to age-matched controls. Additional auditory tests also show deficits in sound source localization, based on temporal and intensity cues. We also observed a statistically significant correlation between the perception of speech in noise, and motoric and cognitive functions. However, a correlation between genetic predisposition (number of triplets) and function of inner ear was not found. CONCLUSIONS We conclude that HD negatively influences the function of the central part of the auditory system at cortical and subcortical levels, altering predominantly speech processing and sound source lateralization. SIGNIFICANCE We have thoroughly characterized auditory pathology in patients with HD that suggests involvement of central auditory and cognitive areas.

Mechanical and Electrical Specifications of the Active Lung Simulator i-Lung – Development of i-Lung 1.0 to i-Lung 2.0

Abstract Lung simulators are important for different application fields like respirator manufacturing processes, teaching purposes as well as environmental and analytical aerosol transport measurements. State-of-the-art lung simulators have a great disadvantage of not taking the internal structure of the human lung into account. Furthermore it is not possible to simulate aerosol exposition to these lung equivalents. To overcome these restrictions and disadvantages, the i-Lung has been developed primarily as an active lung simulator, which can also be used as a passive lung simulator. With the i-Lung it is possible to simulate physiological and pathological breathing patterns with different lung equivalents like latex bags, primed porcine lungs or even fresh porcine lungs. The presented versions 1.0 and 2.0 of the i-Lung are compared in the mechanical and electrical setup. As a development of the i-Lung 1.0, the i-Lung 2.0 provides a refined mechanical construction, more flexible fields of application and an interchangeable dual control unit. The control unit of the lung simulator is either an integrated single based computer (SBC) or the NI cRIO system. With the cRIO control unit, the i-Lung 2.0 is able to perform real time data transmission. Due to the further developments and improvements of the i-Lung system, more physiological and realistic breathing simulation can be executed with the i-Lung 2.0. Thus, the developed lung simulator becomes a real alternative to animal testing. This can be especially interesting for the cosmetic industry, as animal testing has been banned within the EU for the hazardousness and toxicity tests of cosmetic products since March 11 th 2013.

Sensor system development for the novel spontaneous active breathing lung simulator, i-Lung

Breathing simulation is an indispensable task not only for respirator manufacturing processes. Using an active lung simulator including an aerosol measurement system at different working environments would provide information about the actual aerosol exposure to the respiratory tract of the employees at their specific working places. For this purpose a sensor system is being developed to enhance the options of use of the novel lung simulator i-Lung. The sensor system is designed to gather environmental and simulation specific parameters. The enhancement of the i-Lung module by integrating a sensor system including sensors for temperature, pressure, flow and humidity enlarges the field of potential applications of the simulator. This development is seen as further step in direction of a certification as alternative to animal models and as an essential pre-commercial development of the i-Lung system.