Environmental noise affects auditory temporal processing development and NMDA-2B receptor expression in auditory cortex

Abstract

Auditory temporal processing is essential for sound discrimination and speech comprehension. Under normal developmental conditions, temporal processing acuity improves with age. As recent animal studies have shown that the functional development of the auditory cortex (AC) is impaired by early life exposure to environmental noise (i.e., continuous, moderate-level, white noise), here we investigated whether the normal age-related improvement in temporal processing acuity is sensitive to delayed development of the AC. We used a behavioral paradigm, the gap-induced prepulse inhibition of the acoustic startle reflex, to assess the gap detection threshold, and provide a comparison of temporal processing acuity between environmental noise-reared rats and age-matched controls. Moreover, because age-related changes normally occur in the relative expression of different N-methyl-D-aspartate (NMDA) receptor subunits, we assessed the level of protein expression of NMDA-2A and 2B receptors (NR2A and NR2B respectively) in the AC after environmental noise-rearing. As hypothesized, rats reared in environmental noise showed (1) poor temporal processing acuity as adults (i.e., gap detection threshold remained elevated at a juvenile-like level), and (2) an increased level of NR2B protein expression compared to age-matched controls. 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 in environmental noise for two months did not affect their already-mature gap detection threshold. Thus, masking normal sound inputs with environmental noise during early life, but not adulthood, impairs temporal processing acuity as assessed with the gap detection threshold.

Figure 1

The spectrum of the environmental noise used in the experiment.

Figure 2

Gap-induced prepulse inhibition (Gap-PPI) of the acoustic startle reflex revealed impaired temporal processing acuity in environmental noise-reared rats. (A) The Gap-PPI% measured in rats reared in environmental noise until 2-months old (N-2m) was significantly lower than that of age-matched controls (C-2m) (two-way ANOVA, ***P<0.0001). (B) At 3-months old, the Gap-PPI% measured in environmental noise-reared rats (N-3m) was also significantly lower than that of a control group (C-3m) (two-way ANOVA, ***P<0.0001). (C) The gap detection threshold in the environmental noise-reared rats was significantly elevated compared to age-matched controls (N-2m vs. C-2m: Student’s t-test, *P = 0.02; N-3m vs. C-3m: Student’s t-test, **P = 0.005).

Figure 3

Temporal processing acuity in environmental noise-reared rats improved after they were housed in a normal acoustic environment. (A) Rats reared in environmental noise until 2-months old demonstrated an increase in Gap-PPI% after an additional 14 days of normal acoustic experience (N-2m+Q14) compared to values recorded immediately after noise-rearing (N-2m) (two-way ANOVA, ** P = 0.001). (B) In rats reared in environmental noise until 2-months old, there was a significant decrease in their gap detection threshold after they were moved to normal acoustic conditions (one-way ANOVA, *P = 0.02), such that the average gap detection decreased from 16 ± 7 ms to 4 ± 1.2 ms after 28 days of normal acoustic experience. (C-D) In rats reared in environmental noise until 3-months old, there was a trend for the average gap detection threshold to decrease following normal acoustic experience (N-3m: 8.6 ± 0.7 ms; N-3m+Q35: 4.7 ± 0.7 ms); however, the Gap-PPI% did not statistically improve (two-way ANOVA, P>0.05) after 14 days of normal acoustic experience.

Figure 4

Environmental noise exposure did not affect temporal processing acuity in normally-reared, adult rats. (A) The Gap-PPI% did not change after 3-month old rats (Pre) were housed in environmental noise for an additional two months (N-2m) (two-way ANOVA, P>0.05). (B) The already-mature average gap detection threshold in normally-reared, adult rats (Pre: 5.0 ± 0.7 ms) was unchanged after environmental noise exposure for 10 days (N-10d), one month (N-1m) or 2 months (N-2m) (one-way ANOVA, P>0.05).

Figure 5

Environmental noise-rearing had a differential effect on NR2A and NR2B protein expression in the auditory cortex (AC). (A and C) Western blotting bands of NR2A (A) and NR2B (C) for six environmental noise-reared rats (band 4–9) and three age-matched controls (band 1–3) (each band represents an individual animal). (B and D) The density ratio of NR2A/β-actin expression in the control and the environmental noise groups did not differ (Student’s t-test, P>0.05; panel B), whereas there was a ~4-fold greater NR2B/β-actin density ratio in the environmental noise-reared rats compared to the age-matched controls (Student’s t-test, F = 10.8, **P < 0.001; panel D).