Cell type-specific and age-related changes in auditory cortical processing

Aging is inevitable and while the age-related deterioration of many brain functions including sensory, cognitive and motor functions are well documented, we know little about age-related changes in cortical processing at the neural circuit level. In particular, it remains unclear how cortical GABAergic interneurons contribute to age-related changes in cortical information processing. To address this issue, it is important to not only discriminate cell types, but also to delineate between central and peripheral effects of aging. In the present study, focusing on the auditory cortex, we investigate how the structure of spontaneous and auditory-evoked population activity changes with age and comparing two mouse strains to distinguish central and peripheral aging effects. We recorded neural ensembles in the auditory cortex of awake C57BL/6J mice, which have a mutation leading to early peripheral age-related hearing loss (ARHL). We observed an age-related decrease in multi-unit spiking activity, with a correlation between increased hearing threshold and increased spontaneous theta oscillations that is not apparent in age-matched CBA/J mice, which do not exhibit early ARHL. Combining electrophysiological and optogenetic approaches in both young and aged mice with and without early ARHL, we further investigate both cell-autonomous and circuit level changes in auditory cortical processing involving GABAergic cells expressing either Parvalbumin or Somatostatin, thereby providing a deeper insight into the underlying mechanisms of age-related changes in auditory function.