Jana Burianová

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.

Age-related changes in calbindin and calretinin immunoreactivity in the central auditory system of the rat.

Age-related changes in the levels of major intracellular calcium buffers are known to occur in different parts of the mammalian brain, including the central auditory pathway. In the present study, we evaluate with immunohistochemistry and the western blot technique the effect that aging has on the calbindin- and calretinin-expressing system of neurons in the higher structures of the central auditory pathway, in the inferior colliculus (IC), medial geniculate body (MGB) and auditory cortex (AC) of two rat strains, the slowly aging Long-Evans and the fast aging Fischer 344. Interestingly, the age-related changes demonstrated a similar character regardless of the rat strain. In the IC of young animals, the majority of calbindin and calretinin immuno-reactive (CB and CR-ir) cells were found in the dorsal and external cortices and only sparse positive cells were present in the central nucleus of the IC. With aging, the number of CB-ir and CR-ir neurons decreased significantly in both the dorsal and external cortices. Furthermore, these declines were accompanied by an age-related reduction in the mean volumes of CB- and CR-ir neuronal somas. In the MGB of young rats, CB-ir neurons were present in abundant numbers in both the dorsal and ventral subdivisions, while CR-ir neurons were practically absent in this structure. With aging, the number and mean volume of CB-ir cells in the ventral subdivision of the MGB were significantly decreased. In comparison with the IC and MGB, age-related numerical and volumetric declines of both CB-ir and CR-ir neurons in the AC were less pronounced. Western blot protein analysis revealed a pronounced age-related decline in the levels of calbindin in both strains and in all examined brain regions. In contrast, the decline in calretinin levels with aging was less prominent, with a significant decline only in the IC of both strains. The observed age-related changes in the calbindin- and calretinin-expressing systems may contribute significantly to the deterioration of hearing function known as central presbycusis.

The response properties of neurons in different fields of the auditory cortex in the rat.

The auditory cortex (AC) of the rat has been the subject of many studies, yet the details of its functional organization are still not well understood. We describe here the functional organization of the AC in young rats (strain Long Evans, aged 30-35 days, anesthetized with ketamine/xylazine) on the basis of the neuronal responses to acoustic stimuli. Based on the neuronal responses to broad band noise (BBN) and pure tone bursts, the AC may be divided into the primary auditory cortex (AI) and three other core fields: anterior (AAF), suprarhinal (SRAF) and posterior (PAF) as well as an unspecific region (UR) inserted between the AI and AAF. The core fields are surrounded by a belt area. Neurons in the AI, AAF, SRAF and PAF showed well defined characteristic frequencies (CF) in response to pure tone stimulation; in contrast, UR neurons responded only at high intensities without a clear CF. Neurons responding only to BBN stimulation were found mostly in the belt area. The putative borders between the core fields were determined by changes in their tonotopic gradient; however, no tonotopic organization was found in the PAF. Neurons with the shortest response latencies to BBN stimulation were found in layer 4 (L4) and layer 6 (L6) in the AI, while those with the longest latencies in the superficial layers (L1/2) of the belt area. Similar principles of responsiveness were observed when the spike rate in response to BBN stimulation was evaluated, with the highest rate present in L4 of the AI and the lowest in L1/2 of the belt area. According to the shape of the peristimulus time histograms, the responses of neurons in the AC of the rat may be classified as pure onset, sustained, onset-sustained, double peak or late onset. The most dominant in all fields, as well as in all layers, was the pure onset response. Our findings offer further cues for understanding the functional organization of the AC in the rat.

The influence of aging on the number of neurons and levels of non-phosporylated neurofilament proteins in the central auditory system of rats.

In the present study, an unbiased stereological method was used to determine the number of all neurons in Nissl stained sections of the inferior colliculus (IC), medial geniculate body (MGB), and auditory cortex (AC) in rats (strains Long Evans and Fischer 344) and their changes with aging. In addition, using the optical fractionator and western blot technique, we also evaluated the number of SMI-32-immunoreactive (-ir) neurons and levels of non-phosphorylated neurofilament proteins in the IC, MGB, AC, and visual cortex of young and old rats of the two strains. The SMI-32 positive neuronal population comprises about 10% of all neurons in the rat IC, MGB, and AC and represents a prevalent population of large neurons with highly myelinated and projecting processes. In both Long Evans and Fischer 344 rats, the total number of neurons in the IC was roughly similar to that in the AC. With aging, we found a rather mild and statistically non-significant decline in the total number of neurons in all three analyzed auditory regions in both rat strains. In contrast to this, the absolute number of SMI-32-ir neurons in both Long Evans and Fischer 344 rats significantly decreased with aging in all the examined structures. The western blot technique also revealed a significant age-related decline in the levels of non-phosphorylated neurofilaments in the auditory brain structures, 30–35%. Our results demonstrate that presbycusis in rats is not likely to be primarily associated with changes in the total number of neurons. On the other hand, the pronounced age-related decline in the number of neurons containing non-phosphorylated neurofilaments as well as their protein levels in the central auditory system may contribute to age-related deterioration of hearing function.

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.

The effect of parvalbumin deficiency on the acoustic startle response and prepulse inhibition in mice

The strength of the acoustic startle response (ASR) to short bursts of broadband noise or tone pips (4, 8 and 16 kHz) and the prepulse inhibition (PPI) of the ASR elicited by prepulse tones (4, 8 and 16 kHz) were measured in parvalbumin-deficient (PV-/-) mice and in age-matched PV+/+ mice as controls. Hearing thresholds as determined from recordings of auditory brainstem responses were found to be similar in both genotypes. The ASRs to broadband noise and tones of low and middle frequencies were stronger than the ASRs in response to high-frequency tones in both groups. In PV-/- mice, we observed smaller ASR amplitudes in response to relatively weak startling stimuli (80-90 dB sound pressure level (SPL)) of either broadband noise or 8-kHz tones compared to those recorded in PV+/+ mice. For these startling stimuli, PV-/- mice had higher ASR thresholds and longer ASR latencies. PPI of the ASR in PV-/- mice was less effective than in PV+/+ mice, for all tested prepulse frequencies (4, 8 or 16 kHz) at 70 dB SPL. Our findings demonstrate no effect of PV deficiency on hearing thresholds in PV-/- mice. However, the frequency-specific differences in the ASR and the significant reduction of PPI of ASR likely reflect specific changes of neuronal circuits, mainly inhibitory, in the auditory centers in PV-deficient mice.

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.

Age-Related Differences in Hearing Function and Cochlear Morphology between Male and Female Fischer 344 Rats

Fischer 344 (F344) rats represent a strain that is frequently used as a model for fast aging. In this study, we systematically compare the hearing function during aging in male and female F344 rats, by recording auditory brainstem responses (ABRs) and distortion product otoacoustic emissions (DPOAEs). In addition to this, the functional parameters are correlated with the cochlear histology. The parameters of the hearing function were not different in the young (3-month-old) male and female F344 rats; the gender differences occurred only in adult and aged animals. In 8–24-month-old males, the ABR thresholds were higher and the ABR amplitudes were smaller than those measured in females of the same age. There were no gender differences in the neural adaptation tested by recording ABRs, elicited by a series of clicks with varying inter-click interval (ICI). Amplitudes of DPOAEs in both the males and females decreased with age, but in the males, the decrease of DPOAE amplitudes was faster. In males older than 20 months, the DPOAEs were practically absent, whereas in 20–24-month-old females, the DPOAEs were still measurable. There were no gender differences in the number of surviving outer hair cells (OHC) and the number of inner hair cell ribbon synapses in aged animals. The main difference was found in the stria vascularis (SV). Whereas the SV was well preserved in females up to the age of 24 months, in most of the age-matched males the SV was evidently deteriorated. The results demonstrate more pronounced age-related changes in the cochlear morphology, hearing thresholds, ABR amplitudes and DPOAE amplitudes in F344 males compared with females.