Abstract
Alterations in inhibitory circuits of the primary auditory cortex (pAC) have been shown to be an aspect of aging and age-related hearing loss (AHL). Several studies reported a decline in parvalbumin (PV) immunoreactivity in aged rodent pAC of animals displaying AHL and conclude a relationship between reduced sensitivity and declined PV immunoreactivity. However, it remains elusive whether AHL or a general molecular aging is causative for decreased PV immunoreactivity. In this study, we aimed to disentangle the effects of AHL and general aging on PV immunoreactivity patterns in inhibitory interneurons of mouse pAC. We compared young and old animals of a mouse line with AHL (C57BL/6) and a mutant (C57B6.CAST-Cdh23Ahl+) that is not vulnerable to AHL according to their hearing status by measuring auditory brainstem responses (ABR) and by an immunohistochemical evaluation of the PV immunoreactivity patterns in two dimensions (rostro-caudal and layer) in the pAC. Although AHL could be confirmed by ABR measurements for the C57BL/6 mice, both aged strains showed a similar reduction of PV+ positive interneurons in both, number and density. The pattern of reduction across the rostro-caudal axis and across cortical layers was similar for both aged lines. Our results demonstrate that a reduced PV immunoreactivity is a sign of general, molecular aging and not related to age related hearing loss.
Significance Statement Deficiency of sensory functions is one of the major detriments of aging. In hearing, aging affects both the periphery and inhibitory circuits in the central system, resulting in hearing loss and altered perception. Centrally, the major subclass of inhibitory interneurons (parvalbumin positive) shows reduced parvalbumin immunoreactivity, which is believed to be related to altered inhibition. Identifying the factor that dominates this decline is important to understand molecular aging in the central auditory system. Here, we demonstrate that the decreased parvalbumin immunoreactivity in the primary auditory cortex of mice is dominated by general aging rather than age-related hearing loss, suggesting that altered cortical inhibition in the auditory system may not be secondary to peripheral changes, but a consequence of aging per se.
Footnotes
Authors declare there are no competing financial interests
This work was supported by the DFG Cluster of Excellence “Hearing4all” [grant number EXC 1077/1].
Lower Saxony State Office for Consumer Protection and Food Safety/LAVES, permission number 33.9-43502-04-13/1271
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