Acoustically Enriched Environment during the Critical Period of Postnatal Development Positively Modulates Gap Detection and Frequency Discrimination Abilities in Adult Rats.

Throughout life, sensory systems adapt to the sensory environment to provide optimal responses to relevant tasks. In the case of a developing system, sensory inputs induce changes that are permanent and detectable up to adulthood. Previously, we have shown that rearing rat pups in a complex acoustic environment (spectrally and temporally modulated sound) from postnatal day 14 (P14) to P28 permanently improves the response characteristics of neurons in the inferior colliculus and auditory cortex, influencing tonotopical arrangement, response thresholds and strength, and frequency selectivity, along with stochasticity and the reproducibility of neuronal spiking patterns. In this study, we used a set of behavioral tests based on a recording of the acoustic startle response (ASR) and its prepulse inhibition (PPI), with the aim to extend the evidence of the persistent beneficial effects of the developmental acoustical enrichment. The enriched animals were generally not more sensitive to startling sounds, and also, their PPI of ASR, induced by noise or pure tone pulses, was comparable to the controls. They did, however, exhibit a more pronounced PPI when the prepulse stimulus was represented either by a change in the frequency of a background tone or by a silent gap in background noise. The differences in the PPI of ASR between the enriched and control animals were significant at lower (55 dB SPL), but not at higher (65-75 dB SPL), intensities of background sound. Thus, rearing pups in the acoustically enriched environment led to an improvement of the frequency resolution and gap detection ability under more difficult testing conditions, i.e., with a worsened stimulus clarity. We confirmed, using behavioral tests, that an acoustically enriched environment during the critical period of development influences the frequency and temporal processing in the auditory system, and these changes persist until adulthood.

Reference hearing thresholds in an extended frequency range as a function of age.

The ISO 7029 (2000) standard defines normative hearing thresholds H (dB hearing level) as a function of age Y (years), given by H = α(Y - 18)(2), up to 8 kHz. The purpose of this study was to determine reference thresholds above 8 kHz. Hearing thresholds were examined using pure-tone audiometry over the extended frequency range 0.125-16 kHz, and the acquired values were used to specify the optimal approximation of the dependence of hearing thresholds on age. A sample of 411 otologically normal men and women 16-70 years of age was measured in both ears using a high-frequency audiometer and Sennheiser HDA 200 headphones. The coefficients of quadratic, linear, polynomial and power-law approximations were calculated using the least-squares fitting procedure. The approximation combining the square function H = α(Y - 18)(2) with a power-law function H = ß(Y - 18)(1.5), both gender-independent, was found to be the most appropriate. Coefficient α was determined at frequencies of 9 kHz (α = 0.021), 10 kHz (α = 0.024), 11.2 kHz (α = 0.029), and coefficient ß at frequencies of 12.5 kHz (ß = 0.24), 14 kHz (ß = 0.32), 16 kHz (ß = 0.36). The results could be used to determine age-dependent normal hearing thresholds in an extended frequency range and to normalize hearing thresholds when comparing participants differing in age.

Effect of Kv3 channel modulators on auditory temporal resolution in aged Fischer 344 rats.

AUT00063 and AUT00202 are novel pharmaceutical modulators of the Kv3 subfamily of voltage-gated K+ channels. Kv3.1 channels, which control fast firing of many central auditory neurons, have been shown to decline with age and this may contribute to age-related deficits in central auditory processing. In the present study, the effects of the two novel compounds that specifically modulate Kv3 channels on auditory temporal processing were examined in aged (19-25-month-old) and young-adult (3-5 month-old) Fischer 344 rats (F344) using a behavioral gap-prepulse inhibition (gap-PPI) paradigm. The acoustic startle response (ASR) and its inhibition induced by a gap in noise were measured before and after drug administration. Hearing thresholds in tested rats were evaluated by the auditory brainstem response (ABR). Aged F344 rats had significantly higher ABR thresholds, lower amplitudes of ASR, and weaker gap-PPI compared with young-adult rats. No influence of AUT00063 and AUT00202 administration was observed on ABR hearing thresholds in rats of both age groups. AUT00063 and AUT00202 had suppressive effect on ASR of F344 rats that was more pronounced with AUT00063. The degree of suppression depended on the dose and age of the rats. Both compounds significantly improved the gap-PPI performance in gap detection tests in aged rats. These results indicate that AUT00063 and AUT00202 may influence intrinsic firing properties of neurons in the central auditory system of aged animals and have the potential to treat aged-related hearing disorders.

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.

Behavioral evaluation of auditory function abnormalities in adult rats with normal hearing thresholds that were exposed to noise during early development.

Noise-exposed rat pups provide a model of early deprivation of sensory input to the central auditory system, allowing the study of developmental neuroplasticity. Our previous results have demonstrated that a brief exposure of rats to broadband noise (125 dB SPL 8 min, 14th postnatal day) at the onset of hearing resulted in an altered intensity perception and frequency discrimination in adulthood despite normal hearing thresholds. In this study, we assessed the gap-detection ability and possible presence of tinnitus- and hyperacusis-like behavior in adult rats after the same neonatal acoustic trauma, using measurements of the acoustic startle response (ASR) in quiet and noisy environments and its prepulse inhibition by gaps in noise (gap-PPI). A significant deficit in the ability to detect gap was observed in the exposed rats when 55 dB SPL broadband noise was used as background. An increase of noise intensity to 65-75 dB SPL led to strengthening of the gap-PPI in exposed animals, which approached the gap-PPI values of control animals at these levels. Behavioral signs of tinnitus (gap detection deficits in 10 kHz narrow band noise) were found in 25% of exposed rats. An increased sensitivity to continuous noise was manifested in all exposed rats by suppression of the ASR at significantly lower background noise levels than in the controls. This effect was particularly pronounced in rats with tinnitus-like behavior. Our results indicate that neonatal acoustic trauma, producing only a transient threshold shift, may produce permanent abnormalities in suprathreshold auditory functions and the development of tinnitus and hyperacusis-like behavior.

Czech Republic 20 years after Chernobyl accident.

The territory of the Czech Republic was contaminated as a result of the breakdown in the Chernobyl nuclear power plant in 1986. The Czech population received low doses of ionising radiation which, though it could not cause a deterministic impact, could have had stochastic effects expressed in the years following the accident. Twenty years after the accident is a long enough time to assess its stochastic effects, primarily tumours and genetic impairment. The moderate amount of radioactive fallout received by the Czech population in 1986 increased thyroid cancer in the following years; on the other hand, no obvious genetic impact was found.

Cooling of the auditory cortex modifies neuronal activity in the inferior colliculus in rats.

There are powerful pathways descending from the auditory cortex (AC) to the inferior colliculus (IC), yet their function is not fully understood. The aim of this study is to examine the effects of a reversible cortical inactivation, achieved by cooling of the AC, on the responses of neurons in the rat IC. Extracellular single-unit or multi-unit activity was recorded in the IC of anaesthetized rats with a 16-channel multielectrode probe introduced along the IC dorso-ventral axis through the dorsal cortex (DCIC) to the central nucleus of the IC (CIC). Cooling of the AC produced an increase in spontaneous activity and magnitude of the sound-evoked response in 47% of the IC neurons. Maximal changes in the neuronal activity were observed in the DCIC and the central part of the CIC. The final segments of the sustained responses to 60 ms stimuli and the off responses were more affected than the onset segments. Inactivation of the AC resulted in a suppression of the post-excitatory inhibition and neuronal adaptation, which was reflected in a pronounced enhancement of synchronized responses to a series of fast repeated clicks. The response parameters recovered, at least partly, to the pre-cooling levels 1 h after the cooling cessation. The frequency tuning properties of the IC neurons did not show any significant changes during the cooling period. The results demonstrate that AC cooling inactivates excitatory corticofugal pathways and results in a less activated intrinsic inhibitory network in the IC.

Responses to species-specific vocalizations in the auditory cortex of awake and anesthetized guinea pigs.

Species-specific vocalizations represent an important acoustical signal that must be decoded in the auditory system of the listener. We were interested in examining to what extent anesthesia may change the process of signal decoding in neurons of the auditory cortex in the guinea pig. With this aim, the multiple-unit activity, either spontaneous or acoustically evoked, was recorded in the auditory cortex of guinea pigs, at first in the awake state and then after the injection of anesthetics (33 mg/kg ketamine with 6.6 mg/kg xylazine). Acoustical stimuli, presented in free-field conditions, consisted of four typical guinea pig calls (purr, chutter, chirp and whistle), a time-reversed version of the whistle and a broad-band noise burst. The administration of anesthesia typically resulted in a decrease in the level of spontaneous activity and in changes in the strength of the neuronal response to acoustical stimuli. The effect of anesthesia was mostly, but not exclusively, suppressive. Diversity in the effects of anesthesia led in some recordings to an enhanced response to one call accompanied by a suppressed response to another call. The temporal pattern of the response to vocalizations was changed in some cases under anesthesia, which may indicate a change in the synaptic input of the recorded neurons. In summary, our results suggest that anesthesia must be considered as an important factor when investigating the processing of complex sounds such as species-specific vocalizations in the auditory cortex.

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.

Frequency discrimination in rats exposed to noise as juveniles.

Sound exposure during the early postnatal period can significantly influence the function of the auditory system in rats during adulthood. In the present study, rat pups (strain Long-Evans) were exposed to broad-band noise at 125dB SPL for 8, 12 or 25min on postnatal day 14 and then at the age of 3-5months their frequency discrimination at 4 and 16kHz was assessed using a modified method of the prepulse inhibition of the acoustic startle reflex. In all groups of exposed rats, an altered frequency discrimination of the tonal stimuli was observed, in comparison with controls, at 70dB SPL. A worsening of frequency discrimination was observed even in animals exposed for 8min, the auditory thresholds of which were almost identical to that of control animals. The individual auditory thresholds did not correlate with frequency discrimination. The difference in frequency discrimination between the exposed and control animals disappeared at 85-90dB SPL. Our data suggests that brief noise exposure during the critical period of development results in the altered frequency discrimination at moderate sound intensities in adult rats, which may appear even in individuals with normal hearing thresholds.

Software for the analysis of species-specific vocalizations.

Vocalization calls are behaviorally relevant complex sounds that typically contain several harmonics and show frequency and amplitude modulation. In this paper, an introduction to a software tool for the analysis of species-specific vocalizations is presented. The algorithm automatically or under user supervision detects time-varying amplitude and frequency parameters, which can serve for the statistical analysis of calls or as the substrate for the manipulation and synthesis of artificial calls. The described program and its results will be used in studying the representation of complex sounds in the central nervous system.

Cortical representation of species-specific vocalizations in Guinea pig.

We investigated the representation of four typical guinea pig vocalizations in the auditory cortex (AI) in anesthetized guinea pigs with the aim to compare cortical data to the data already published for identical calls in subcortical structures - the inferior colliculus (IC) and medial geniculate body (MGB). Like the subcortical neurons also cortical neurons typically responded to many calls with a time-locked response to one or more temporal elements of the calls. The neuronal response patterns in the AI correlated well with the sound temporal envelope of chirp (an isolated short phrase), but correlated less well in the case of chutter and whistle (longer calls) or purr (a call with a fast repetition rate of phrases). Neuronal rate vs. characteristic frequency profiles provided only a coarse representation of the calls' frequency spectra. A comparison between the activity in the AI and those of subcortical structures showed a different transformation of the neuronal response patterns from the IC to the AI for individual calls: i) while the temporal representation of chirp remained unchanged, the representations of whistle and chutter were transformed at the thalamic level and the response to purr at the cortical level; ii) for the wideband calls (whistle, chirp) the rate representation of the call spectra was preserved in the AI and MGB at the level present in the IC, while in the case of low-frequency calls (chutter, purr), the representation was less precise in the AI and MGB than in the IC; iii) the difference in the response strength to natural and time-reversed whistle was found to be smaller in the AI than in the IC or MGB.

Age-related changes in auditory temporal processing in the rat.

Presbycusis, as the deterioration of hearing ability occurring with aging, can be manifested not only in a shift of hearing thresholds, but also in a deterioration of the temporal processing of acoustical signals, which may in elderly people result in degraded speech comprehension. In this study we assessed the age-related changes in the temporal processing of acoustical signals in the auditory system of pigmented rats (Long Evans strain). The temporal resolution was investigated in young adult (3-4 months) and old (30-34 months) rats by behavioral and electrophysiological methods: the rats' ability to detect and discriminate gaps in a continuous noise was examined behaviorally, and the amplitude-rate function was assessed for the middle latency response (MLR) to clicks. A worsening of the temporal resolution with aging was observed in the results of all tests. The values of the gap detection threshold (GDT) and the gap duration difference limen (GDDL) in old rats increased about two-fold in comparison with young adult rats. The MLR to a click train in old rats exhibited a significantly faster reduction in amplitude with an increasing stimulation rate in comparison with young adult rats. None of the age-related changes in the parameters characterizing temporal resolution (GDT, GDDL and MLR to a click train) correlated with the degree of the age-related hearing loss. However, the age-related changes in MLR amplitude-rate function correlated with the age-related changes in GDDL, but not with the changes in GDT. The behavioral and electrophysiological data clearly show that aging in rats is accompanied with a pronounced deficit in the temporal processing of acoustical signals that is associated with the deteriorated function of the central auditory system.

Inactivation of the left auditory cortex impairs temporal discrimination in the rat.

The left auditory cortex (AC) in humans is involved in the processing of the temporal parameters of acoustical signals, specifically in speech perception, whereas the right AC plays the dominant role in pitch and melody perception. The hemispheric lateralization of acoustical signal processing in non-human mammals is less explored. The present study examined the ability of rats to detect or discriminate a series of gaps in continuous noise under conditions of unilateral or bilateral reversible inactivation of the AC. The results showed that muscimol-induced reversible inactivation of the left AC suppresses the ability of rats to discriminate between acoustical stimuli of different temporal parameters (duration or repetition rate), whereas inactivation of the right AC results in no change or only a mild decrease in discrimination ability. Hemispheric asymmetry was observed only in the case of gap discrimination tasks, but not in a gap detection task. Our findings demonstrate that, similarly as in humans, the left AC in the rat plays the dominant role in temporal discrimination. These data provide further evidence for the functional asymmetry of the mammalian brain, which appears in a relatively early phase of evolution.

Representation of species-specific vocalizations in the medial geniculate body of the guinea pig.

Individual nuclei of the auditory pathway contribute in a specific way to the processing of complex acoustical signals. We investigated the responses of single neurons to typical guinea pig vocalizations (purr, chutter, chirp and whistle) in the ventral part of the medial geniculate body (MGB) of anesthetized guinea pigs. The neuronal and population peristimulus time histograms (PSTHs) reflected the repetition frequency of individual phrases in the calls. The patterns of PSTHs correlated well with the sound temporal envelope in calls with short phrases (purr, chirp). The dominant onset character of the neuronal responses resulted in a lower correlation between the sound envelope and the PSTH pattern in the case of longer calls (chutter and whistle). A time-reversed version of whistle elicited on average a 13% weaker response than did the natural whistle. The rate-characteristic frequency (CF) profile provided only a coarse representation of the sound frequency spectrum without detailed information about the individual spectral peaks and their relative magnitudes. In comparison with the inferior colliculus (Suta et al. in J Neurophysiol 90:3794-3808, 2003), the processing of species-specific vocalizations in the MGB differs in: (1) a less precise representation of the temporal envelope in the case of longer calls, but not in the case of calls consisting of one or more short phrases; (2) a less precise rate-CF representation of the spectral envelope in the case of low-frequency calls, but not in the case of broad-band calls; (3) a smaller difference between the responses to natural and time-reversed whistle.

Effect of auditory cortex lesions on the discrimination of frequency-modulated tones in rats.

The lateralization of functions to individual hemispheres of the mammalian brain remains, with the exception of the human brain, unresolved. The aim of this work was to investigate the ability to discriminate between falling and rising frequency-modulated (FM) stimuli in rats with unilateral or bilateral lesions of the auditory cortex (AC). Using an avoidance conditioning procedure, thirsty rats were trained to drink in the presence of a rising FM tone and to stop drinking when a falling FM tone was presented. Rats with a lesion of the AC were able to learn to discriminate between rising and falling FM tones; however, they performed significantly worse than did control rats. A greater deficit in the ability to discriminate the direction of frequency modulation was observed in rats with a right or bilateral AC lesion. The discrimination performance (DP) in these rats was significantly worse than the DP in rats with a left AC lesion. Animals with a right or bilateral AC lesion improved their DP mainly by recognizing the pitch at the beginning of the stimuli. The lesioning of the AC in trained animals caused a significant decrease in DP, down to chance levels. Retraining resulted in a significant increase in DP in rats with a left AC lesion; animals with a right lesion improved only slightly. The results demonstrate a hemispheric asymmetry of the rat AC in the recognition of FM stimuli and indicate the dominance of the right AC in the discrimination of the direction of frequency modulation.

Representation of species-specific vocalizations in the inferior colliculus of the guinea pig.

The responses of individual neurons to 4 typical guinea pig vocalization calls (purr, chutter, chirp, and whistle) were recorded in the inferior colliculus (IC) of anesthetized guinea pigs. All calls elicited a response in about 80% of units. Unit selectivity for individual calls was low, given that a majority of neurons (55% of 124 units) responded to all vocalizations and only a small portion of neurons (3%) responded to only one call or did not respond to any of the calls (3%). In 15% of units, the response to one call was > or =25% stronger than the response to any other sound (tone, noise, and other calls); these neurons were selective for chirp or whistle, and no unit preferred chutter or purr. Neuronal activity provided information about the spectrotemporal patterns of the calls. Peristimulus time histograms (PSTHs) reflected the energy of the near-characteristic frequency band, and the population PSTH reliably matched the sound envelope for calls characterized by one or more short impulses (chirp, purr, and chutter) but did not exactly fit the envelope for whistle--a slow-modulated and relatively long call. Calculations based on firing rates indicated the approximate positions of the main spectral peaks but did not always reflect their relative magnitude. The time-reversed version of whistle elicited on average a weaker response than did the natural whistle (by 24%), but there were neurons with a significantly stronger response to the natural ("forward-selective," 30%) as well as to the time-reversed whistle ("reverse-selective," 15%). This study does not prove the existence of units selectively responding to animal calls, but it provides evidence for the encoding of the spectrotemporal acoustic patterns of vocalizations by IC units.