Altered response dynamics and increased population correlation to tonal stimuli embedded in noise in aging auditory cortex.

Abstract

Age-related hearing loss (presbycusis) is a chronic health condition that affects 1/3 of the world s population. One hallmark of presbycusis is a difficulty hearing in noisy environments. Presbycusis can be separated into two components: alterations of peripheral mechanotransduction of sound in the cochlea, and central alterations of auditory processing areas of the brain. While the effects of the aging cochlea in hearing loss have been well studied, the role of the aging brain in hearing loss is less well understood. Therefore, to examine how age-related central processing changes affect hearing in noisy environments, we used a mouse model (Thy1-GCaMP6s X CBA mice) that has excellent peripheral hearing in old age. We used in vivo 2-photon Ca2+ imaging to measure the responses of neuronal populations in auditory cortex (ACtx) of adult (2-6 months, 9 male, 6 female, 4,180 neurons) and aging (15-17 months, 6 male, 3 female, 1055 neurons) while listening to tones in noisy backgrounds. We found that ACtx neurons in aging mice showed larger responses to tones and have less suppressed responses consistent with reduced inhibition. Aging neurons also showed less sensitivity to temporal changes. Population analysis showed that neurons in aging mice showed higher pairwise activity correlations and showed a reduced diversity in their responses to sound stimuli. Using neural decoding techniques, we show a loss of information in neuronal populations in the aging brain. Thus, aging not only affects the responses of single neurons but also affects how these neurons jointly represent stimuli.Significance Statement:Aging results in hearing deficits particularly under challenging listening conditions. We show that auditory cortex contains distinct subpopulations of excitatory neurons that preferentially encode different stimulus features and that aging selectively reduces certain subpopulations. We also show that aging increases correlated activity between neurons, and thereby reduces the response diversity in auditory cortex. The loss of population response diversity leads to a decrease of stimulus information and deficits in sound encoding, especially in noisy backgrounds. Future work determining the identities of circuits affected by aging could provide new targets for therapeutic strategies.