The effect of acoustically enriched environment on structure and function of the developing auditory system

It has long been known that environmental conditions, particularly during development, affect morphological and functional properties of the brain including sensory systems; manipulating the environment thus represents a viable way to explore experience-dependent plasticity of the brain as well as of sensory systems. In this review, we summarize our experience with the effects of acoustically enriched environment (AEE) consisting of spectrally and temporally modulated complex sounds applied during first weeks of the postnatal development in rats and compare it with the related knowledge from the literature. Compared to controls, rats exposed to AEE showed in neurons of several parts of the auditory system differences in the dendritic length and in number of spines and spine density. The AEE exposure permanently influenced neuronal representation of the sound frequency and intensity resulting in lower excitatory thresholds, increased frequency selectivity and steeper rate-intensity functions. These changes were present both in the neurons of the inferior colliculus and the auditory cortex (AC). In addition, the AEE changed the responsiveness of AC neurons to frequency modulated, and also to a lesser extent, amplitude-modulated stimuli. Rearing rat pups in AEE leads to an increased reliability of acoustical responses of AC neurons, affecting both the rate and the temporal codes. At the level of individual spikes, the discharge patterns of individual neurons show a higher degree of similarity across stimulus repetitions. Behaviorally, rearing pups in AEE resulted in an improvement in the frequency resolution and gap detection ability under conditions with a worsened stimulus clarity. Altogether, the results of experiments show that the exposure to AEE during the critical developmental period influences the frequency and temporal processing in the auditory system, and these changes persist until adulthood. The results may serve for interpretation of the effects of the application of enriched acoustical environment in human neonatal medicine, especially in the case of care for preterm born children.


Introduction
The brain retains its experience-dependent plasticity during the whole lifespan (Alwis and Rajan, 2014;de Villers-Sidani and Merzenich, 2011).However, the influence of environmental conditions is most profound during early ontogenesis, and normal development of brain and sensory perception depends upon optimal environmental stimulation (van Praag et al., 2000).This finding holds in general, yet particular effects of environmental conditions may be observed in individual sensory pathways including the auditory system.
In the auditory domain, the experience-dependent plasticity has been investigated using a variety of paradigms, ranging from passive exposure to simple stimuli to complex environments incorporating multimodal active interactions.In the case of the simple stimuli, such as tone pips or narrow-band noises, the exposure usually leads to tonotopical remodeling or augmented representation of the given stimulus (Miyakawa et al., 2013;Oliver et al., 2011;Poon et al., 1990;Zhang et al., 2001); it is therefore questionable whether this type of intervention may be considered to be an enrichment, as the resulting alterations are probably not very beneficial from the ethological point of view (Han et al., 2007), see also below.On the other hand, rearing animals in more complex acoustic environments results in generalized and non-specific morphologic and functional changes of the auditory system (Bureš et al., 2014;Engineer et al., 2004;Jakkamsetti et al., 2012).These manifest themselves, for example, by altered gene expression (Rampon et al., 2000), increased dendritic length, volume, and spine density (Globus et al., 1973;Svobodová Burianová and Syka, 2020), increased cortical thickness (Diamond et al., 1966), altered frequency and intensity representation both in subcortical and cortical neurons (Bureš et al., 2014;Engineer et al., 2004;Pysanenko et al., 2018), altered temporal processing and neuronal synchrony (Bureš et al., 2018;Jakkamsetti et al., 2012;Percaccio et al., 2005), or altered spatial selectivity (Cai et al., 2009;Zhang et al., 2009).A positive influence of environmental enrichment has been observed also in cochlear hair cells and their ribbon synapses (Chang et al., 2018).
The changes observed at the neuronal level are often accompanied by alterations in perception: improved frequency discrimination ability and improved ability to detect a short gap in noise (Pysanenko et al., 2021), enhanced performance in detecting vocalizations in noise (Homma et al., 2020), enhanced spatial learning (Hendershott et al., 2016), or different startle reactivity and prepulse inhibition efficacy (Varty et al., 2000;Willott and Turner, 1999).Interesting is the report that environmental enrichment prolongs the natural lifespan (Yamashita et al., 2018).
Importantly, several studies on animals showed that the influence of the enriched environment is dependent on the attention and activity of the subjects: the effect of the same environment was different depending on whether the animal was only passively exposed to the stimulation orconverselypaid attention to the stimulus or was allowed/required to interact with the environment (Bureš et al., 2014;Ferchmin and Bennett, 1975;Polley et al., 2006;Recanzone et al., 1993).
In the former case, the experience-dependent plastic changes were only weak or non-existent, while active participation of the subjects evoked larger changessometimes the magnitude of alterations was actually associated with the amount of activity of individual animals (Bureš et al., 2014).
Another important aspect is the design of the environmental enrichment in order to have positive outcomes.First, the intensity of the acoustic stimuli must not be too high as it could induce effects similar to acoustic trauma.The optimum intensity should be determined according to the respective situation, in particular, with respect to hearing thresholds and purpose of the enrichment: for example, restoration of noise-induced auditory processing disorder in adulthood may require higher stimulus levels than enrichment during ontogenesis.Furthermore, the contents of the stimulus should be sufficiently richwideband, modulated both in frequency and in amplitude, and random in many aspects.In other cases, the observed effects might be rather detrimental: selective reorganization of neuronal circuits, elevated neuronal excitatory thresholds, widened frequency tuning curves, or impaired auditory detection and discrimination ability (Bureš et al., 2017;Han et al., 2007;Rybalko et al., 2019Rybalko et al., , 2015;;Zhang et al., 2001;Zheng, 2012).
The auditory system is particularly sensitive to environmental conditions during a developmental phase often denoted as critical period (CP), which follows after the onset of hearing and its duration is in the order of days or weeks, depending on the anatomical structure and species.In rats and mice, the onset of hearing occurs approximately on P12 and the cortical CP lasts approximately four weeks.Furthermore, it has been shown that the CP is not uniform and consists of distinct phases dedicated to development of different acoustic features (Bhumika et al., 2020;de Villers-Sidani and Merzenich, 2011;Insanally et al., 2009).It is not clear, however, if such phasing is present also in subcortical structures and in the periphery.In humans the situation is different: fetuses start to hear at 20 weeks of gestational age and the development of auditory perception continues until 10 years of age (Sanes and Woolley, 2011).Moreover, the newborn human brain is initially very sensitive to acoustic differences, however, with time, it specializes and remains sensitive only to distinctive features of phonemes in their mother language (Kral, 2013).In addition, important critical role plays development of language that is limited to first several postnatal years.Studies with cochlear implants investigating speech comprehension as a function of implantation age found that critical period for successful therapy expires at approximately 3 years (Kral et al., 2019).
Importantly, it has been shown that proper structural and functional maturation of auditory centers depends on the appropriate inputs during the CP (Gabriele et al., 2000;Kandler and Gillespie, 2005;Zhang et al., 2001).However, not only that the auditory system is more sensitive to the surrounding conditions during the CP: the characteristics of the acoustic environment may affect the auditory system differently when applied during the CP and in adulthood (Bureš et al., 2014;Engineer et al., 2004;Percaccio et al., 2007).Specifically, the enrichment during the CP appears to have persistent and generalized effects, while the effects of an enrichment after the CP closure may be temporary, specific to only certain neuronal subpopulations, or even non-existent (Bureš et al., 2014;Noreña and Eggermont, 2005;Zhang et al., 2009).Interestingly, certain effects of enrichment could be observed even if the acoustic stimulation is delivered before the hearing onset.In these cases, the surrounding sound is probably transmitted to the cochlea via bone conduction and thereby influences the sensorineural development -ABR responses to bone-conducted stimuli could be recorded already on postnatal day 7 in the rat pups (Geal-Dor et al., 1993).
It is generally accepted that the mechanisms by which acoustical enrichment affects the development of central auditory system are based on modulation of neuronal innervation and refinement of synaptic connectivity (de Villers-Sidani et al., 2007;Froemke and Jones, 2011;Gabriele et al., 2000;Kandler and Gillespie, 2005;Zhang et al., 2001).In the case of auditory periphery, however, the mechanisms are less clear.Chang et al. (2018), who observed sound-driven increase in prestin expression in the cochlear outer hair cells and also accelerated maturation of ribbon synapses in the inner hair cells, speculate that these alterations could be due to thyroid hormone, retinoid nuclear transcription factor, GATA-3, and Pou4f3, nevertheless, further studies are needed to unravel the exact mechanisms.
As stated above, an appropriately designed enriched environment applied to intact or healthy subjects can improve general characteristics of both neuronal reponses and behavioral capabilities compared to animals housed in standard conditions.In addition, numerous studies have shown that the application of enriched environment also has the power to reverse the consequences of an acoustic trauma, stress, or another disadvantageous condition such as side-effects of drug administration, social isolation, or hyperacusis (Alwis and Rajan, 2014;Chen et al., 2010;Cheng et al., 2023;Dziorny et al., 2021;Green et al., 2017;Jiang et al., 2015;Marchetto et al., 2021;Noreña and Chery-Croze, 2007;Noreña andEggermont, 2006, 2005;Sturm et al., 2017;Willott et al., 2005Willott et al., , 2000;;Zhu et al., 2014).This paper reviews and discusses the current knowledge of how enriched environment influences structural and functional properties of the auditory system.We focus particularly on the acoustically enriched environment (AEE) applied to intact, healthy animals during their early ontogeny.Included are the results of electrophysiological, morphological, and behavioral experiments on laboratory animals.In addition, we briefly review present knowledge how to ameliorate with the aid of AEE the negative impacts of a noise exposure on the auditory system as well as implications of the reported findings for human neonatal medicine.
The exposure to simple stimuli such as narrow-band noise bursts, tone pips or frequency-modulated tones often changes the distribution of neuronal characteristic frequencies and tonotopical organization, manifested as exaggerated representation of the frequency of the exposure tone, degraded tonotopy, and impaired frequency selectivity both in cortical and subcortical structures (Oliver et al., 2011;Poon et al., 1990;Zhang et al., 2001;Zheng, 2012).For example, early exposure of rat pups to pulsed tones resulted in accelerated emergence and an expansion of A1 representations of those specific tone frequencies, as well as a deteriorated tonotopicity and broader-than-normal receptive fields (Zhang et al., 2001).Oliver et al. (2011) showed that an augmented acoustical environment applied during postnatal days P9-P28 resulted in a decreased latency and complicated alterations of response magnitudes depending on the neuronal best frequency, the intensity of the measuring stimulus, and the relationship of the measuring stimulus frequency to the AEE frequency.At lower levels of the auditory pathway, however, exposure to simple stimuli may act in a beneficial direction: Chang et al. (2018) exposed mouse pups to frequency-enriched acoustic environments in postnatal days P0-P14.They found that the use of acoustic environment significantly decreased thresholds of the auditory brainstem responses, increased the expression of prestin in outer hair cells, and accelerated maturation of ribbon synapses in inner hair cells.Interestingly, the effects of the same stimulus may differ for auditory cortex and subcortical structures: Miyakawa et al. (2013) reported that early pulsed-tone exposure (from P9 to P25) had persistent influence on tonotopic arrangement of the auditory cortex and no effect on cortical tuning bandwidths, while the inferior colliculus neurons showed transient alterations of tuning bandwidths and no change of tonotopy.
Alterations reported for exposures with simple sounds are mostly related to frequency contents of the exposure stimulus.In contrast, application of a more complex environment has the power to change neuronal responses in a non-specific manner, affecting a wide range of characteristic frequencies with no direct relationship to the spectral contents of the encompassing acoustic field.The enhanced environments found in the available literature are of several different types.
The works of Engineer et al. (2004) and Jakkamsetti et al. (2012) used environment that was enriched in a multimodal way and comprised tonal stimuli, complex stimuli including sounds of nature and music, and interactions of the animals with sound-triggering elements and rewards.Other works employed purely acoustic enrichment.For example, Bao et al. (2013) used natural sounds of jungle, while Bureš et al. (2014Bureš et al. ( , 2018)), Pysanenko et al. (2018), andHomma et al. (2020) used an artificial wideband spectrally and temporally modulated stimulus sometimes denoted as rippled noise.
Animals exposed postnatally to a complex AEE often exhibited narrower tuning bandwidths of auditory neurons, indicating a higher frequency selectivity (Bureš et al., 2014;Engineer et al., 2004;Jakkamsetti et al., 2012;Miyakawa et al., 2013;Pysanenko et al., 2018).This effect was observed in various parts of the auditory system: in the inferior colliculus (Bureš et al., 2014), in the primary auditory cortex (Engineer et al., 2004;Pysanenko et al., 2018), and in the posterior auditory field (Jakkamsetti et al., 2012).In certain cases, a more elaborate acoustic environment resulted in complex alterations of neuronal receptive fields related to the stimulus characteristics.In particular, Bao et al. (2013), who reared rats in a naturalistic, complex acoustic environment, observed that cortical neurons became more selective to spectrotemporal features of the exposure sounds, and that more neurons were involved in representing the whole set of complex sounds and fewer neurons responded to each individual sound, but with greater magnitudes.Homma et al. (2020) described a shift of neuronal receptive field preferences to optimally extract information in noisy environments: rearing rat pups between P6 and P45 in several types of broadband dynamic rippled noises (at 60dB SPL) resulted in reduction of neuronal responsiveness to noise backgrounds having statistics similar to the exposure noise.In addition, further behavioral training shifted the neuronal receptive fields toward the trained foreground sound, altogether resulting in higher signal-detection performance (see also section Behavioral capabilities).
An exposure to a complex AEE affects also neuronal processing of sound intensity.Bureš et al. (2014) and Pysanenko et al. (2018) reported lowered excitatory thresholds both in the inferior colliculus and in the primary auditory cortex.These changes were observed irrespective of the neuronal characteristic frequency and spanned the entire hearing range.Besides shifted thresholds, alterations were found also at suprathreshold levels: the populations of auditory neurons in the enriched animals had a higher proportion of monotonic rate-intensity functions and the shapes of these functions were different.Importantly, the existence and/or magnitude of changes was associated with the activity of the animals in a stimulus-detection taska higher activity led to more profound changes.Acoustic enrichment can also alter neuronal response magnitudes and spontaneous activity (Bureš et al., 2014;Engineer et al., 2004;Oliver et al., 2011;Pysanenko et al., 2018).In the inferior colliculus, increased response magnitudes were reported by Bureš et al. (2014).In the auditory cortex, differential observations were made: Pysanenko et al. (2018) found decreased response magnitudes, while Engineer et al. (2004) found increased response strength; these differences are most probably due to very different experimental paradigms of the cited works.
Several studies investigated the influence of AEE on auditory temporal processing.Pysanenko et al. (2018) reported different modulation-transfer functions evoked by frequency-modulated tones: the functions in the enriched animals were less steep, suggesting that these animals were less selective to different modulation frequencies than the controls.When analysing the temporal course of neuronal discharge rate in response to a modulated stimulus, the enriched animals appeared to have a stronger onset relative to the remainder of the response.With respect to the temporal code, neuronal synchrony and phase-locking to periodic stimulus has been shown to be improved by AEE exposure (Bureš et al., 2018;Jakkamsetti et al., 2012); a more complex repetition-rate-dependent alteration of phase-locking ability was reported by Ranasinghe et al. (2012).In addition, Bureš et al. (2018) found that for a repetitive stimulus, the neurons exhibit a lower spike count variance, indicating a more stable rate coding, and the discharge patterns of individual neurons show a higher degree of similarity across stimulus repetitions.
Other specific effects of an acoustically enriched environment applied during early ontogenesis include reduced response latency (Engineer et al., 2004), or increased directional sensitivity (Cai et al., 2009;Zhang et al., 2009).

Behavioral capabilities
Changes at the neuronal level induced by exposure to AEE during the developmental period that include improved response strength, threshold, selectivity, and latency of the inferior colliculus and auditory cortex neurons, enhanced physiological plasticity in the auditory cortex, and refined decoding performance of vocalizations embedded in noise in the A1 neurons, suggests that AEE applied during development is likely to have impact on the auditory behavior (see also summary in Table 2).
Several studies indicate that a complex form of enrichment, including both acoustic and non-acoustic stimulation, can enhance performance in sound discrimination tests and mitigate the effects of early noise exposure in rats.Rats raised from the postnatal day P10 to day P56 in a complex environmental stimulation showed increased directional sensitivity, improved number of correct scores, decreased reaction time and azimuth deviation in sound-azimuth discrimination test (Cai et al., 2009).Application of a complex enriched environment for approximately four weeks after developmental noise exposure in rats almost restored disrupted sound frequency discrimination (Zhu et al., 2014, see later).In these cases, however, the environment included complex multimodal stimulation (i.e., not only acoustic clues): cages contained running wheels, seesaws, balls, tunnels, cubes and cone toys, and also stairs, ramps and platforms and decorations.Only few studies report about behavioral outcomes stemming exclusively from the exposure to an acoustically enriched environment during the CP.Xu et al. (2009) used an early auditory enrichment (from postnatal day 14) of rat pups with a classical music.They demonstrated that in different sound durationdiscrimination tasks, the music-exposed rats acquired the behavior faster than the control rats, supporting the hypothesis that an early auditory enrichment with music enhances learning ability in auditory signal-detection task and in sound duration-discrimination task.
However, changes induced by an early acoustic exposure observable at the neuronal level are not always manifested behaviorally.Ranasinghe et al. (2012) reared rats during their postnatal development (from day 9 through day 38) in either a pulsed-noise stimulus or speech sounds.Despite the finding that the early exposure to pulsed-noise input made A1 neurons better in following temporally modulated broadband stimuli at 10 Hz, it did not significantly change either neural or behavioral discrimination of speech compared to control rats, suggesting that speech sound processing is resistant to changes in simple neural response properties caused by manipulating early acoustic environment.
Rearing animals in the presence of moderately loud modulated noise during the auditory CP proved to be advantageous.Homma et al. (2020) raised rat pups between P6 and P45 in several types of broadband dynamic rippled noises (at about 60dB SPL) followed by training in a vocalization-in-noise detection task.
They found that noise-rearing can improve adult vocalization-in-noise detection performance; the highest benefit of exposure occurred in backgrounds similar to the exposure noise, yet certain benefit of noise-rearing was present regardless of the statistics of the noise used for exposure.Zheng et al. (2012) used an exposure of rats between P60 and P90 to continuous white noise at ca. 65dB SPL and found that fine (but not coarse) pitch discrimination was impaired in the exposed rats, but their behavioral performance in noisy background was significantly better compared to the unexposed controls, suggesting an adaptation to noisy conditions.
In our behavioral experiments, rat pups were exposed to an AEE reinforced with an active behavioral feedback for two weeks starting on postnatal day P14 (Pysanenko et al., 2021).The AEE consisted of a broad-band amplitude-modulated rippled noise with a temporally variable sinusoidal spectral envelope presented at 55 dB SPL.With the aim to attract the animals' attention to the acoustic stimulation, the noise background was supplemented with several types of embedded target sounds appearing randomly in time at 60 dB SPL, with one of them (frequency-modulated tone) triggering the release of a reward.In adult rats we measured the startle (acoustic startle response, ASR) reactivity and prepulse inhibition (PPI) of ASR with several prepulse stimuli, in order to compare their sensation of sound intensity, frequency discrimination and gap detection ability.The enriched animals were generally not more sensitive to startling sounds, also their PPI of ASR induced by noise or pure tone pulses was comparable to controls.However, they exhibited a more pronounced PPI when the prepulse stimulus was represented either by a change in the frequency of the continuous background tone or a gap in the background noise.Significant differences in the PPI of ASR between the enriched and control animals were present only at lower (55dB SPL) intensities of the background sound.With intensities of the background noise of 65 dB or more the differences disappeared.Thus, our experimental design of the developmental acoustically enriched environment led to an improvement of the frequency resolution and gap detection ability under difficult testing conditions with a worsened stimulus clarity.

Morphologic alterations
The beneficial effects of rearing animals in a multisensory enriched environment on neuronal morphology have been described in several studies (see Table 3).The references can be traced back to the seminal observations of Globus et al. (1973), Greenough et al. (1973), and Diamond et al. (1976), where increased dendritic branching, dendritic length, and spine density in various cortical brain areas were described.For example, Wistar rat pups, 21 days old, that were housed in enriched conditions (10 animals in a large cage with toys and a running wheel) showed in adulthood in comparison with controls increased dendritic arborisation as well as increased density of dendritic spines in layer-III parietal pyramidal neurons (Leggio et al., 2005).However, studies limited to effects of AEE are sparse.Bose et al. (2010) reported the effects of housing of rats in AEE during the 5-week post-weaning period on the auditory cortex.They observed longer basal dendrites of neurons in the layers II/III of AI with their larger arborization as measured by Sholl analysis, and a higher spine density on both basal and apical dendrites of A1 neurons in comparison with controls.Svobodová Burianová and Syka (2020) analyzed changes occurring in the neurons of inferior colliculus, medial geniculate body and auditory cortex of rats exposed to AEE.Using an experimental paradigm with an active perception of AEE during P14-28 (see also section Behavioral capabilities), they reported a complex effect of the enrichment on neuronal morphology in the above mentioned parts of the auditory pathway.AEE promoted neuronal branching and increase in the soma size, particularly in the external and central cortices of the inferior colliculus, with less prominent effect on the dorsal IC cortex.Interestingly, AEE did not change dendritic length or complexity of arborization in the medial geniculate body but significantly increased spine density on dendrites of these neurons.The results from the auditory cortex confirmed the observation of Bose et al. ( 2010) that rearing animals in AEE results in a prolongation of basal dendrites of pyramidal neurons.In principle, it may be expected that the effects of AEE during the CP would be opposite to the auditory deprivation, but this is not entirely true.If rats are exposed briefly (8 min) to a very loud sound (125 dB) on postnatal day P14, which temporarily elevates auditory thresholds for 2-3 weeks, thereby demonstrating restricted auditory input, the dendritic length of neurons in the central cortex of the inferior colliculus is increased, paralleling the effect of AEE (Ouda et al., 2012).The underlying mechanism remains unresolved.It is worth noting that AEE can affect the morphology of neurons outside the canonical auditory pathway.Recent studies have revealed that alterations in the auditory input can exert a notable influence on the function of the hippocampus (Zhang et al., 2021).Traumatic sound exposure has been found to suppress hippocampal neurogenesis (Kraus et al, 2010).
Nevertheless, investigations into the specific effects of AEE on this brain structure have not been conducted to date.

Recovery from hearing loss induced by acoustical enriched environment.
It has been shown previously that application of the AEE in adult animals immediately after noise exposure can significantly alleviate the negative effects of the noise exposure.For example, Norena and Eggermont (2005) found that cats exposed to a traumatizing noise and immediately thereafter placed for a few weeks into an enriched acoustic environment (tone-pips of random frequency between 0.625 and 20 kHz, 80 dB SPL) presented a much-restricted hearing loss compared with controls that were placed for the same time into a quiet environment.The enriched environment in this case spectrally matched the expected hearing loss range (6 to 32 kHz with the largest loss from 24 to 32 kHz).The hearing loss in the enriched-environment cats was restricted to 6-8 kHz with 16 -32 kHz having normal thresholds.Interestingly, the plastic tonotopic map changes in the primary auditory cortex that appears usually as a result of noise exposure could no longer be demonstrated.Zhu et al. (2014) who reared developmentally noise-exposed Sprague Dawley rats (on postnatal day 10-38) in an acoustic-enriched environment (pure tone pips, 1 pps, frequencies 1-30 kHz, 65 dB SPL) for ∼4 weeks found that environmental acoustic enrichment nearly restored to normal the behavioral deficit resulting from early disrupted acoustic inputs.They observed that signs of degraded frequency selectivity of neurons as measured by the bandwidth of frequency tuning curves and decreased long-term potentiation of field potentials recorded in the primary auditory cortex of these noise-exposed rats were partially reversed.Jiang et al. (2015) were determined to find out whether postnatal noise exposure impairs neural temporal resolution in the auditory cortex in rat, and, if so, whether environmental enrichment can rescue this degraded neural temporal acuity.They used the neural gap detection threshold in anesthetized rats as an index of temporal acuity and found that exposure of juvenile rats to moderate-level noise induced much higher neural gap detection thresholds in adulthood than exposure of adult rats to the same noise.When the rats with early noise exposure (during postnatal days 10-30) were reared thereafter for 26 days in an enriched environment (tones with a duration of 100 ms, occurring once in 2 seconds, frequency between 5 kHz and 20 kHz presented in a pseudorandom manner, 70 dB SPL) a recovery from the noise-induced degraded neural temporal resolution appeared.Similar experiments were performed by Sturm et al. (2017) in mice.The authors found that brief noise overexposure performed at postnatal days 20-23 (band-pass noise with a 1 kHz bandwidth that was centered at 16 kHz and presented at 116 dB SPL for 45 min) leads to distinct reorganizations of excitatory and inhibitory synaptic inputs onto glutamatergic and GABAergic neurons in the inferior colliculus and that the nature of these reorganizations correlates with animals' impairments in detecting brief sound gaps.Acoustic stimulation (pulsed white noise at 75 dB SPL) delivered immediately after noise exposure and continued for 7 days prevented circuit reorganizations and gap detection deficits.
All these experimental results highlight the potential for using sound therapy soon after a noise exposure to prevent the development of central processing deficits.The therapy in the form of a continuous exposure to sound must be applied immediately after noise exposure with a duration of weeks, with a variable frequency and intensity that does not damage the cochlea but is possible to induce positive changes in the central parts of the auditory system.

Implications for human neonatal medicine
Human fetuses start to respond to sound at 20 weeks of gestational age, first to low frequency sounds around 500 Hz (Hepper and Shahidullah, 1994;Vogelsang et al., 2023).Early auditory experiences can essentially influence brain development.Brain maturation in preterm infants may be affected by the auditory environment of the neonatal intensive care unit.Some studies show that in very preterm children premature termination of the intrauterine environment by preterm birth may reduce cortical development in a dose-dependent manner, providing a neural substrate for functional impairment (Kapellou et al., 2006).According to Forbes et al. (2020), hypoxic damage to the developing brain due to preterm birth causes many anatomical changes, including damage to the periventricular white matter.Northam et al. (2012) found that injury to major intra-or interhemispheric white matter pathways connecting frontal and temporal language regions occurring in very preterm children may be connected with prevalence of language problems later in their life.Similarly, Reidy et al. (2013) who investigated language abilities in children born very preterm at 7 years of age found that white matter abnormalities were accompanied with difficulties in phonological awareness, semantics, grammar, and discourse.Sanchez et al. (2020) confirmed that children born before 30 weeks' gestation had poorer language than children born at term.
In addition, besides suggesting the rules how to limit occurrence of noise in the environment of neonatal intensive care units, including incubators, several authors proposed what should be the optimal acoustical environment for preterm born children.The mother's voice and heartbeat sounds elicit auditory plasticity in the human brain before full gestation (Webb et al., 2015).These authors examined infants born extremely prematurely (between 25-and 32-wk gestation) in the first month of life.Newborns were randomized to receive auditory enrichment in the form of audio recordings of maternal sounds (including their mother's voice and heartbeat) or routine exposure to hospital environmental noise.Cranial ultrasonography measurements were performed at 30 ± 3 d of life.Results showed that newborns exposed to maternal sounds had a significantly larger auditory cortex bilaterally compared with control newborns receiving standard care.The effects of live maternal speaking and singing on physiological parameters of preterm infants in the newborn intensive care unit were shown already some time ago by Filippa et al. (2013), who tested the hypothesis that vocal stimulation can have differential effects on preterm infants at a behavioural level.Comparisons of periods with and without maternal vocal stimulation revealed in preterm infants significantly greater oxygen saturation level and heart rate and significantly fewer negative critical events.In another study (Haslbeck et al., 2020) preterm children born at gestational age less than 32 weeks were systematically exposed to creative music therapy based on infant-directed humming and singing in lullaby style.Later investigation of resting-state MRI revealed lower thalamocortical processing delay, stronger functional networks, and higher functional integration in predominantly left prefrontal, supplementary motor, and inferior temporal brain regions in infants treated with music therapy.These studies show that the quality of the structure and function of the auditory system in children born preterm can be influenced by exposing them to an acoustical environment that can have positive effect on the development of their sensory systems and brain.It has to be mentioned that modern therapeutic approaches can ameliorate, at least partially, the negative effects of the exposure to a harsh environment of the world outside of the maternal environment in preterm children.Robertson et al. (2022) studied outcomes of language comprehension, production, and vocabulary in children born preterm that acquired cochlear implants.They found that the mean language development scores after 5 years of cochlear implant use are only slightly below corresponding means of children born at term with implants.As commented by Kral (2022), the importance of the study is in the evidence of the long-term benefit of cochlear implants in children born preterm with severe-to-profound hearing loss.More details about the topic of hearing and language development with respect of cochlear implants and critical periods is available in Kral et al. (2019).

Open Questions in the Field and Future Directions
Most experiments with AEE influence on the auditory function were performed, so far, on rats.This species offers wealth of behavioral tests and in addition, hearing in this species starts 11-12 days postnatally.Similar start of hearing is present in mice but information about AEE effects in mouse are so far limited.
Because of a possibility to manipulate genome in mice, large information about mouse genetic data available, and a possibility to study brain activity in awake animals on cellular and subcellular level, we can expect that more experiments will be performed in this species in future.
Differences in the timing of the development of hearing function between the rat and man complicate the interpretation of data obtained in animal experiments in human medicine.In normally born children we can start to influence the auditory development by acoustical stimulation at the time when the auditory system already has been in function for about 20 weeks.Precise acoustical stimulation of the fetus in the mother´s womb is difficult.Therefore, the data from animal experiments have validity especially for preterm children.
An open question, that certainly deserves investigation, remains optimal acoustical composition of the sounds used for AEE.Very probably sounds similar to human language will be used, containing frequency and amplitude-modulated sounds of a modest intensity.In the meantime, the results of experimental research will inform us to what extent such AEE is influencing auditory cortex and to what extent subcortical parts of the auditory system.We will learn what AEE changes are present at molecular level, at synapses and in neuronal nets and by this way we will be able to optimize the acoustical stimulation.
One application of the AEE cannot be forgotten since its influence will be even more important in the futurethe application as a therapy of pathological states after noise exposure.The aim will be to find optimal healing of the organ of Corti and other damaged inner ear structures and to recover their function.

Conclusions
First postnatal weeks in rats and mice represent a period of fast developmental changes of the auditory system that is characterized by an instability, the result of which can be both negative and positive changes of the structure and function of the auditory system, depending on parameters of the sound surrounding the animals.Acoustically enriched environment represents environment the intention of which is to induce positive developmental effects either in the sense of normal development or even with an enhanced quality of the function.Mild sound intensity, variable frequency and duration of usually several weeks characterize the sound parameters used as the enriched environments, the positive effects of which are evident in the function of the auditory system in adult animals.Lower hearing thresholds, sharper tuning curves of neurons, differences in the processing of sound intensity and time parameters of the sound are the rewards of the application of AEE that can be even used for an amelioration of the negative effects of a sound exposure during the developmental period.The knowledge of the developmental plasticity and the ways how to influence it in a positive way can be used in the human medicine and education, particularly in preterm infants.

Table 1 .
Summary of reports on the effects of enriched environment on neuronal responses.

Table 2 .
Summary of reports on the effects of enriched environment on behavioral capabilities.

Table 3 .
Summary of reports on the effects of enriched environment on neuronal morphology.total length and volume of the basal dendritic segments of pyramidal neurons and the number and density of spines; elevated number of spines and spine density in nonpyramidal neurons MGB: increased spine density IC: increased mean dendritic length and volume, and the soma surface in the external cortex and the central nucleus of the IC