Abstract
Age-related hearing loss (presbycusis) affects one-third of the world's population. One hallmark of presbycusis is difficulty hearing in noisy environments. Presbycusis can be separated into two components: the aging ear and the aging brain. To date, the role of the aging brain in presbycusis is not well understood. Activity in the primary auditory cortex (A1) during a behavioral task is because of a combination of responses representing the acoustic stimuli, attentional gain, and behavioral choice. Disruptions in any of these aspects can lead to decreased auditory processing. To investigate how these distinct components are disrupted in aging, we performedin vivo2-photon Ca2+imaging in both male and female mice (Thy1-GCaMP6s×CBA/CaJmice) that retain peripheral hearing into old age. We imaged A1 neurons of young adult (2-6 months) and old mice (16-24 months) during a tone detection task in broadband noise. While young mice performed well, old mice performed worse at low signal-to-noise ratios. Calcium imaging showed that old animals have increased prestimulus activity, reduced attentional gain, and increased noise correlations. Increased correlations in old animals exist regardless of cell tuning and behavioral outcome, and these correlated networks exist over a much larger portion of cortical space. Neural decoding techniques suggest that this prestimulus activity is predictive of old animals making early responses. Together, our results suggest a model in which old animals have higher and more correlated prestimulus activity and cannot fully suppress this activity, leading to the decreased representation of targets among distracting stimuli.SIGNIFICANCE STATEMENTAging inhibits the ability to hear clearly in noisy environments. We show that the aging auditory cortex is unable to fully suppress its responses to background noise. During an auditory behavior, fewer neurons were suppressed in the old relative to young animals, which leads to higher prestimulus activity and more false alarms. We show that this excess activity additionally leads to increased correlations between neurons, reducing the amount of relevant stimulus information in the auditory cortex. Future work identifying the lost circuits that are responsible for proper background suppression could provide new targets for therapeutic strategies to preserve auditory processing ability into old age.
Funder
HHS | NIH | National Institute on Aging
HHS | NIH | National Institute on Deafness and Other Communication Disorders
Cited by
4 articles.
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