Frequency- and level-dependent changes in auditory brainstem responses (ABRs) in developing mice
Representative examples of ABR waveforms obtained in response to the stimuli indicated at the top of each column illustrate the evolution of waveform morphology during the period of functional development (i.e., P12–P18 and P60). Two overlapping replicates are shown at each age. Stimulus levels in dB are designated in terms of both sensation level (SL) and sound pressure level (SPL). For animals older than P14, SPL was the highest stimulus exposure level. Asterisks associated with P15 waveforms identify wave IV, a response feature that can be difficult to identify in isolated response waveforms as it emerges from the broader wave III/IV typically observed in younger mice. Wave I is identified by filled circles for all ages in panel (a); the peak at P12 preceding wave I is the summating potential.
The duration of ABR waves I (●) and IV (엯) elicited by tone pips [panel (a)] and tone pips [panel (b)] decreased during the period of active, rapid development. Duration was calculated by subtracting peak minima representing the leading and trailing “edges” of both waves I and IV (i.e., subtracting the latencies corresponding to the “valleys” preceding and following each wave peak). Lines represent exponential fits to the data. Values for ranged from 0.69 to 0.80.
The percentage of individuals that responded at the maximum output of the sound system for all stimulus frequencies tested is shown with age as parameter. At P12, the majority of mice responded to stimuli between 2 and but not to higher frequencies. Developmental changes occurred generally between P12 and P13 for stimuli and between P13 and P15 at higher stimulus frequencies.
Average threshold versus frequency curves reveal the progressive increase in sensitivity observed between P12 and P18. The responsive bandwidth also increased between P12 and P14. Thresholds to click stimuli are also shown. Standard errors of the mean are indicated for each group. Thresholds obtained from P24 through P90 were pooled and served as adult values. Thresholds at all ages below P18 were significantly different from adults , except for those obtained at P15 in response to . Thresholds acquired at P18 did not differ significantly from those of adults.
(a) and (b) Examples of ABR thresholds plotted as a function of postnatal age are shown for responses to [panel (a)] and [panel (b)]. Dotted lines represent decaying exponentials of the form and are fitted to values between birth and 90 postnatal days. Parameters for the fit are , , and for the data shown in panel (a) and 54.2, 4432, and 0.35, respectively, for the data shown in panel (b). (c) Slopes of least-squares linear regressions fitted to threshold-age values between birth and P15 (shown as solid lines in panels (a) and (b) are plotted as a function of stimulus frequency and the slope computed for responses to click stimuli is also shown. Values for ranged between and the average was 0.78. Slopes and intercepts computed for each stimulus condition were statistically significant . (d) Time course of threshold development estimated from exponential fits indicated in the form of adjusted time constants [time constant (TC) plus age of first response to airborne sound] is plotted as a function of stimulus frequency and for click stimuli. values computed from the fit ranged between and and the average was 0.85.
(a)–(c) ABR wave latencies obtained in response to clicks (a), (b), and (c) tone bursts presented at SPL are plotted as a function of postnatal age. Solid lines represent decaying exponentials fitted to ABR waves I–IV using a least-squares procedure. Values for ranged from 0.88 to 0.89, 0.76 to 0.90, and 0.63 to 0.89 for the fits shown in panels (a)–(c), respectively. (d) Asymptotic values derived from exponential fits shown in (a)–(c) and at other stimulus frequencies studied are shown for each wave. (e) The rate of latency maturation was determined by comparing time constants derived from exponential fits and adjusted by adding the postnatal age at which responses were first observed at SPL. The rate of threshold maturation versus stimulus frequency is replotted from Fig. 5(d) for comparison. (f) The overall range over which latencies improved during development was determined by subtracting latency estimates measured in response to SPL on P14 from latency estimates observed in adults.
(a)–(c) Mean latencies of wave I recorded using stimuli presented at fixed sensation levels (SL; filled symbols) and at fixed sound pressure levels (SPL; open symbols) are plotted as a function of age for (a), (b), and click (c) stimuli. Hatched areas represent latency improvement differences that could not be accounted for based on threshold elevation, a value referred to as latency residue in this study. (d) Latency residue observed in response to stimuli presented at a constant SPL was computed by subtracting asymptotic latency values associated with responses to SPL stimuli from those associated with the appropriate SL condition and is plotted as a function of frequency.
Average ABR wave I amplitudes elicited by clicks [(a) and (b)] and tone bursts [(c) and (d)] increased during the active, rapid phase of development then decreased to adult levels near the end of the first postnatal month. Developmental changes in amplitudes are shown for stimuli presented at fixed sound pressure levels [SPL; panels (a) and (c)] and at fixed sensation levels [SL; panels (b) and (d)]. Amplitudes measured at P24 differed significantly from those acquired at older ages for the following stimulus conditions: click stimuli at SPL and SL; at SPL and SL .
The rate of wave I amplitude growth during development was computed from the linear growth phase (P12–P24) based on linear regression analysis and plotted as a function of stimulus frequency. Amplitude growth rates were determined using fixed sound pressure levels indicated in the symbol key. Growth rates are shown for click stimuli also. Note the change in the scale of the ordinate.
Wave I latencies are plotted as a function of stimulus level for responses to (a), (b), (c), and (d) at the specified ages. Latency-level curves shown for P14 and younger are from individual animals and those shown from animals at older ages are averaged across individuals to increase the clarity of the figure. Standard deviations are shown for responses at P15, P18, and . Based on statistical tests performed for groups in response to stimuli between 60 and SPL [panel (a)], 50 and SPL [panels (b) and (c)], and 70 and SPL [panel (d)], latencies remained significantly elevated compared to adult values at P15 for all frequencies tested, and although still somewhat elevated at P18, latencies differed significantly from adults for the following conditions: at 50, 70, and SPL; at 50, 60, 80, and SPL.
(a) Changes in the slope of wave I latency versus level functions estimated throughout the period of rapid development mature in a frequency-specific manner, with mature relationships occurring earliest for mid-frequency stimuli, followed by high-frequency stimuli, and last for low-frequency stimuli. Slope estimates were based on linear regression analysis of normalized latency-level curves acquired from individuals. The hatched area above and below the solid line represents standard deviation of the mean slopes determined for the adult group . Standard deviations are also shown for responses obtained at P18. The unfilled triangle represents a single measurement. Slopes of latency-level curves were significantly different from those of adults at P12 for ; at P13 for ; at P14 for , , and for click stimuli; and at P15 for . Slope estimates acquired at P18 did not differ significantly from those of adults. (b) Examples of slopes of latency-level curves from which average slope estimates were used in panel (a) are plotted as a function of age in the right column for three stimulus frequencies: 32, 11.3, and .
Interpeak intervals between waves I and II (a) and central conduction times [CCT; panel (b)] are plotted as a function of stimulus level for responses to at the specified ages. CCT was estimated as the interval between waves I and IV. Individual curves are shown for animals at P13 and P14, and average curves are shown for animals at P15 and older. Based on statistical tests performed for animals in response to stimuli between 50 and SPL, the wave I-II interval remained significantly elevated compared to adult values for P15, P18, and P24 at SPL, and for P15 at 50 and SPL. CCTs were significantly elevated compared to adult values for P15, P18, and P24 at SPL and for P15 at SPL.
Wave I amplitude values are plotted as a function of stimulus level for responses to (a), (b), (c), and (d) at the specified ages. Curves from individuals are shown for animals at P14 and younger, and average curves are shown for animals at P15 and older. Error bars are plotted for the responses at P15 and P24 and represent the standard deviation. Based on statistical tests performed for animals in response to stimuli between 60 and SPL [panel (a)], 40 and SPL [panel (b) and (c)], and 50 and SPL [panel (d)], amplitudes measured at P24 were elevated significantly compared to adult values for the following conditions: at SPL, at SPL, at SPL, and at SPL.
(a) Changes in the slope of wave I amplitude versus level functions estimated throughout the period of rapid development occur in a frequency-specific manner, with mature relationships occurring earlier for high-frequency stimuli and last for low-frequency stimuli. Slope estimates were based on linear regression analysis of the near threshold portion of amplitude-level curves. Hatched areas above and below the solid line represent standard deviation of the mean slopes (slope 1) determined for the adult group . For comparison, the slope of the upper leg of the amplitude-level curve (slope 2) was computed for adults and is also shown . Error bars are plotted for responses at P18 and represent standard deviations. The open triangle (P12) represents a single measurement. Slopes of amplitude-level curves were significantly different from those of adults at P13 and P14 for and at P15 for . Slope estimates acquired at P18 did not differ significantly from those of adults. (b) Examples of amplitude-level slope versus age plots from which average slope estimates were used in this analysis are shown at the top for three stimulus frequencies: 2.8, 11.3, and . (c) An example of an adult amplitude-level curve indicating the lower (near threshold, slope 1) and upper (slope 2) legs is shown in the lower right panel, along with a line fitted to each segment.
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