The present study provides an investigation of the effect of environmental noise-rearing (i.e., continuous, moderate-level, white noise) on 1) temporal processing acuity assessed behaviorally, and 2) NMDA receptor subunit (NR2A and NR2B) protein expression in the AC. As hypothesized, rats exposed to environmental noise during early postnatal life (from 7-days to 2- or 3-months old) showed poor temporal processing acuity as adults (i.e., gap detection threshold remained elevated at a juvenile-like level), as well as an increased level of NR2B protein expression compared to age-matched controls. Additional testing revealed that this poor temporal processing acuity represented delayed development rather than permanent impairment, as moving these environmental noise-reared rats to normal acoustic conditions improved their gap detection threshold to an age-appropriate level. Furthermore, housing normally-reared, adult rats (3-months old) in environmental noise for 2 months did not affect their already-mature gap detection threshold. Collectively, our results suggest that masking normal sound inputs with environmental noise during early life, but not adulthood, impairs temporal processing acuity as assessed with the gap detection threshold.
Behavioral studies on both humans and rats have shown that temporal processing acuity improves during normal development, such that both adult humans [22
] and rats [21
] demonstrate a gap detection threshold of ~5 ms. The results from our adult control rats are consistent with this age-related decrease in gap detection threshold (P-2m: 6 ±2 ms; P-3m: 3.4 ± 1.9 ms). In contrast, rats reared in environmental noise for 2 months had a gap detection threshold of ~17 ms, which is comparable to that of juvenile rats (15-days old) reared in a normal acoustic environment [21
]. Thus, the masking of salient sound inputs with environmental noise during early postnatal life prevented the normal maturation of temporal processing acuity. Of the multiple regions within the central auditory pathway that contribute to temporal processing acuity, previous studies have highlighted the critical importance of the AC. For example, cortical insults, such as transient deactivation [27
] and surgical ablation of the AC [28
], as well as developmental cortical malformation (e.g., microgyria) [29
] have been shown to disrupt temporal processing acuity as assessed by the Gap-PPI paradigm. These findings, coupled with the present results and those of other studies (discussed below), lead us to suggest that the poor temporal processing acuity caused by environmental noise-rearing is associated with a delayed development of the AC.
Normal maturation of the AC is characterized by a progressive refinement of the spectral and temporal response properties of its constituent neurons. For example, electrophysiological studies on developing rats have revealed that the progression to adulthood is marked by an increased frequency-selectivity of neurons in the primary AC (i.e., neurons become more narrowly-tuned) [30
] and an increased cortical ability to respond to high-rate acoustic stimuli, suggestive of improved temporal processing [1
]. Exposing juvenile rats to environmental noise causes neurons in their AC to have sluggish temporal response properties [1
]. However, similar to the present study in which gap detection threshold improved when the environmental noise-reared rats were moved to normal acoustic conditions (), AC neurons showed an improved ability to respond to high-rate acoustic stimuli after environmental noise exposure ceased [1
]. These “rescue” experiments suggest that the poor temporal processing caused by environmental noise represents a developmental delay, not an irreversible impairment. Further support for this suggestion is based on our finding that temporal processing acuity was not impaired in rats exposed to environmental noise as adults. Instead, the already-matured gap detection threshold of the adult rats remained at a normal level following 2 months of environmental noise exposure (i.e., ~5 ms; ). Taken together, our results suggest that the functional maturation of temporal processing acuity can be delayed by masking normal sound inputs with environmental noise during early life.
In addition to the delayed development of temporal processing acuity (present findings) and excitatory response properties of AC neurons [1
], environmental noise-rearing preserves the heightened, juvenile-like plasticity properties of the AC. For example, compared to adult controls, rats raised in environmental noise until adulthood demonstrated elevated levels of LTP induced by thalamocortical activation [9
]. This LTP enhancement was critically-dependent on NR2B subunit activation, as local application of NR2B subunit antagonists blocked the effect [9
]. Consequently, the authors proposed that environmental noise-induced changes in the subunit composition of NMDA receptors, such as the possible maintenance of higher NR2B subunit levels, attenuation of the increase in NR2A subunit levels, or a combination of these two factors, could underlie the increased plasticity they observed [9
]. In the present study, the environmental noise-reared rats had an elevated level of NR2B subunit protein expression in the AC compared to age-matched controls (), despite no difference in NR2A subunit levels (). Thus, our results suggest that the heightened AC plasticity associated with early life exposure to environmental noise may be mediated by the maintenance of juvenile-like levels of NR2B subunit expression. In contrast, during the preparation of our manuscript, Xu et al. reported that rearing rats in environmental noise had no effect on the expression levels of NMDA receptors [14
]. We are uncertain if differences in the experimental procedures, such as tissue preparation, animal age, or antibody sensitivity, contributed to the conflicting results between the two studies. Interestingly, consistent with the suggestion that environmental noise rearing prevents the maturation of the AC, Xu et al. [14
] found that early environmental noise exposure altered the expression of subunits of the GABA-A receptor, indicative of a return to its juvenile form.
It has been proposed that environmental factors which preserve the AC in a state of immaturity, such as the masking of salient sound inputs with noise, may potentially contribute to language developmental delays in children [13
]. The findings of the present study are consistent with this proposal, as we observed that, in addition to arresting AC development (i.e., an elevated NR2B subunit protein expression), environmental noise-rearing resulted in poor temporal processing acuity, which has been linked to impaired language development. Put simply, children with poor temporal processing acuity are more likely to develop poorer language ability than the children with better temporal processing resolution [20
]. Given this relationship, the delayed maturation of temporal processing acuity observed in the present study confirms that environmental noise exposure poses a risk for abnormal child development. Finally, although we found that the cessation of environmental noise exposure yielded a prompt improvement in temporal processing acuity (), the long-term implication of such exposure on language ability remains to be determined.