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.

• MeSH
• akustická stimulace MeSH
• draslíkové kanály Shaw MeSH
• krysa rodu rattus MeSH
• potkani inbrední F344 MeSH
• prepulsní inhibice MeSH
• sluchová percepce * MeSH
• sluchové kmenové evokované potenciály * MeSH
• sluchový práh MeSH
• úleková reakce MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

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.

• MeSH
• akustická stimulace metody   MeSH
• kritické období (psychologie) * MeSH
• krysa rodu rattus MeSH
• novorozená zvířata MeSH
• potkani Long-Evans MeSH
• rozlišení výšky zvuku fyziologie   MeSH
• sluchová percepce fyziologie   MeSH
• sluchové kmenové evokované potenciály fyziologie   MeSH
• úleková reakce fyziologie   MeSH
• věkové faktory MeSH
• životní prostředí * MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

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.

• MeSH
• chování zvířat * MeSH
• hluk škodlivé účinky   MeSH
• hyperakuze etiologie   psychologie   MeSH
• krysa rodu rattus MeSH
• nedoslýchavost z hluku psychologie   MeSH
• neuroplasticita MeSH
• poruchy sluchu etiologie   psychologie   MeSH
• potkani Long-Evans MeSH
• sluchový práh * MeSH
• těhotenství MeSH
• tinnitus etiologie   psychologie   MeSH
• úleková reakce MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

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.

• MeSH
• akustická stimulace MeSH
• časové faktory MeSH
• colliculus inferior metabolismus   patologie   patofyziologie   MeSH
• fyziologická adaptace MeSH
• GABAergní neurony metabolismus   MeSH
• nervový útlum MeSH
• potkani Long-Evans MeSH
• sluchová dráha patofyziologie   MeSH
• sluchové evokované potenciály MeSH
• sluchové korové centrum metabolismus   patologie   patofyziologie   MeSH
• terapeutická hypotermie * MeSH
• termoregulace * MeSH
• zvířata MeSH
• Check Tag
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• srovnávací studie MeSH

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.

• MeSH
• akustická stimulace škodlivé účinky   MeSH
• kochlea cytologie   růst a vývoj   MeSH
• potkani Long-Evans MeSH
• senzorické prahy fyziologie   MeSH
• sluchová percepce fyziologie   MeSH
• sluchové kmenové evokované potenciály fyziologie   MeSH
• sluchové testy MeSH
• synapse fyziologie   MeSH
• úleková reakce fyziologie   MeSH
• zvířata MeSH
• Check Tag
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

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.

• MeSH
• akustická stimulace MeSH
• analýza rozptylu MeSH
• časové faktory MeSH
• elektroencefalografie MeSH
• hluk * MeSH
• krysa rodu rattus MeSH
• novorozená zvířata MeSH
• potkani Long-Evans MeSH
• prepulsní inhibice fyziologie   MeSH
• psychoakustika MeSH
• sluchové kmenové evokované potenciály fyziologie   MeSH
• sluchový práh fyziologie   MeSH
• úleková reakce fyziologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

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 = β(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 β at frequencies of 12.5 kHz (β = 0.24), 14 kHz (β = 0.32), 16 kHz (β = 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.

• MeSH
• akustická stimulace MeSH
• audiometrie čistými tóny normy   MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• lineární modely MeSH
• metoda nejmenších čtverců MeSH
• mladiství MeSH
• mladý dospělý MeSH
• referenční hodnoty MeSH
• senioři MeSH
• sluch * MeSH
• sluchový práh * MeSH
• stárnutí psychologie   MeSH
• věkové faktory MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

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.

• MeSH
• akustická stimulace MeSH
• druhová specificita MeSH
• morčata MeSH
• neurony fyziologie   MeSH
• sluchové evokované potenciály MeSH
• sluchové korové centrum fyziologie   MeSH
• vokalizace zvířat fyziologie   MeSH
• zvířata MeSH
• Check Tag
• morčata MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

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.

• MeSH
• akustická stimulace MeSH
• diskriminační učení MeSH
• krysa rodu rattus MeSH
• potkani Long-Evans MeSH
• presbyakuze patofyziologie   MeSH
• sluchové evokované potenciály MeSH
• sluchový práh fyziologie   MeSH
• stárnutí fyziologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

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.

• MeSH
• akustická stimulace metody   MeSH
• centrální poruchy sluchu chemicky indukované   komplikace   MeSH
• diskriminace (psychologie) fyziologie   MeSH
• elektrický šok škodlivé účinky   MeSH
• funkční lateralita fyziologie   MeSH
• GABA agonisté škodlivé účinky   MeSH
• klasické podmiňování fyziologie   MeSH
• krysa rodu rattus MeSH
• modely nemocí na zvířatech MeSH
• muscimol škodlivé účinky   MeSH
• poruchy sluchové percepce etiologie   MeSH
• sluchové korové centrum účinky léků   fyziologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH