Shaping the aging brain: role of auditory input patterns in the emergence of auditory cortical impairments

Abstract

Age-related impairments in the primary auditory cortex (A1) include poor tuning selectivity, neural desynchronization, and degraded responses to low-probability sounds. These changes have been largely attributed to reduced inhibition in the aged brain, and are thought to contribute to substantial hearing impairment in both humans and animals. Since many of these changes can be partially reversed with auditory training, it has been speculated that they might not be purely degenerative, but might rather represent negative plastic adjustments to noisy or distorted auditory signals reaching the brain. To test this hypothesis, we examined the impact of exposing young adult rats to 8 weeks of low-grade broadband noise on several aspects of A1 function and structure. We then characterized the same A1 elements in aging rats for comparison. We found that the impact of noise exposure on A1 tuning selectivity, temporal processing of auditory signal and responses to oddball tones was almost indistinguishable from the effect of natural aging. Moreover, noise exposure resulted in a reduction in the population of parvalbumin inhibitory interneurons and cortical myelin as previously documented in the aged group. Most of these changes reversed after returning the rats to a quiet environment. These results support the hypothesis that age-related changes in A1 have a strong activity-dependent component and indicate that the presence or absence of clear auditory input patterns might be a key factor in sustaining adult A1 function.

Keywords: A1; GABA; aging; auditory; inhibition; noise; parvalbumin; plasticity.

Figure 1

Changes in frequency representation in the noise-exposed and aged A1. (A) Representative A1 CF maps from the young (Y), young noise-exposed (Y-NE) and aged (A) experimental groups. (B) Representative cortical receptive fields (RFs) obtained for the neurons recorded in the center of the bolded polygons in the respective maps shown in A. (C) Average BW10 for all neurons recorded in each group and separated by CF. (D) CF of A1 neurons plotted against position on the normalized tonotopic axis of the corresponding recorded cortical site (all cortical sites pooled for each group). The average tonotopic index (TI) calculated for each individual A1 maps is shown (see Methods). Y: n = 6, 317 neurons; Y-NE: n = 5, 246 neurons; A: n = 6, 295 neurons. ^*p < 0.05, ^**p < 0.01: t-test.

Figure 2

Impact of noise exposure on spectro-temporal interactions. (A) Representative spatio-temporal receptive fields (STRFs) obtained for single neurons in A1 in Y, Y-NE, and A groups. Positive (red, black dotted line) regions of the STRF indicate that stimulus energy at that frequency and time tended to increase the neuron's firing rate, and negative (blue, white dotted line) regions indicate where the stimulus envelope induced a decrease in firing rate. Note the smaller and shallower inhibitory areas in the aged noise-exposed and aged groups. (B) Total average strengths of activation, inhibition, and activation/inhibition ratio of the STRFs recorded. Note the increase in the activation/inhibition ratio in the Y-NE and A groups. (C) Average latency to maximal activation and inhibition in all experimental groups. (Y, number of STRFs recorded = 275; Y-NE = 208; A = 245). ^*p < 0.05, ^**p < 0.01: t-test.

Figure 3

Reduced A1 neural synchrony in noise-exposed and aged groups. (A) Mean cross-correlation functions for all A1 neuron pairs with inter-neuronal distances less than 0.5 mm in Y, Y-NE, and A groups. (B) Z-score of neuronal firing synchrony (see Methods) as a function of distance for site pairs for all experimental groups. (C) Average time lag in absolute values of the peak of the cross-correlation function for all recorded pairs. (Y, number of site pairs: n = 513; Y-NE, n = 237; A, n = 263).

Figure 4

Reduced deviant tone detection by A1 neurons in the noise-exposed group. (A) Representative normalized responses of individual A1 neurons in the three experimental groups to standards (black line) and deviant tones or “oddballs” (gray line) as a function tone position in the stimulus sequence. The red dotted line represents the asymptote of the progressively suppressed response to standards. (B) Average asymptote computed for the response to oddballs and standards in all groups. Note the reduction in the difference between standards and oddball responses at steady state in the Y-NE and A groups (height of red vertical lines). (C) Average receiving operating characteristic curves computed from responses of individual neurons to oddball tone trains in all groups and for different time points in the tone sequence. AUC stands for “area under the curve.” Note that Y-NE and A groups do not reach the discrimination criterion (70%) (Y, number of neurons recorded = 275; Y-NE = 208; A = 245). ^*p < 0.05, ^**p < 0.01: t-test.

Figure 5

Noise-induced changes in A1 PV+ interneurons and myelin. Quantitative analysis of the average number in A1 of GABA and PV immunoreactive cells per high power field (hpf) and myelin basic protein (MBP) immunoreactivity in all experimental groups. (A) Representative high power photomicrographs of representative sections in all groups. (B) Average PV+ and GABA+ cell counts and average MBP staining fluorescence optical density in all groups (all layers averaged). Note the relative decrease in PV+ cell count and MBP staining in Y-NE and A groups. Number of hemispheres examined: Y = 8, Y-NE = 8, A = 10. ^*p < 0.05, ^**p < 0.01: t-test. Scale bar: 50 μm.

Figure 6

Progressive recovery of A1 alterations after noise discontinuation. (A) Representative RFs of A1 neurons in the Y-NE and young recovered (Y-R) groups. (B), Average BW10 in Y-NE and Y-R groups (all recorded neurons pooled). (C), Representative high power photomicrographs showing immunoreactivity to PV and MBP in Y-NE and Y-R. (D), Quantitative analysis of the average number of PV+ cells and myelin density per high power field in all layers in the Y-R group, Y-NE and Y groups for comparison. Y: n = 6, neurons = 317; Y-NE: n = 5, neurons = 246, and Y-R: n = 4, neurons = 198. Number of hemispheres examined: Y = 8, Y-NE = 8, Y-R = 4. ^*p < 0.05, ^**p < 0.01. Scale bar: 50 μm.