Age-related changes in excitatory and inhibitory intra-cortical circuits in auditory cortex of C57Bl/6 mice

Abstract

A common impairment in aging is age-related hearing loss (presbycusis), which manifests as impaired spectrotemporal processing. Aging is accompanied by alteration in normal inhibitory (GABA) neurotransmission, and changes in excitatory (NMDA and AMPA) synapses in the auditory cortex (ACtx). However, the circuits affected by these synaptic changes remain unknown. Mice of the C57Bl/6J strain show premature age-related hearing loss and changes in functional responses in ACtx. We thus investigated how auditory cortical microcircuits change with age by comparing young (∼ 6 weeks) and aged (>1 year old) C57Bl/6J mice. We performed laser scanning photostimulation (LSPS) combined with whole-cell patch clamp recordings from Layer (L) 2/3 cells in primary auditory cortex (A1) of young adult and aged C57Bl/6J mice. We found that L2/3 cells in aged C57Bl/6J mice display functional hypoconnectivity of both excitatory and inhibitory circuits. Compared to cells from young C57Bl/6 mice, cells from aged C57Bl/6J mice have fewer excitatory connections with weaker connection strength. Whereas young adult and aged C57Bl/6J mice have similar amounts of inhibitory connections, the strength of local inhibition is weaker in the aged group. We confirmed these results by recording miniature excitatory (mEPSCs) and inhibitory synaptic currents (mIPSCs). Our results suggest a specific reduction in excitatory and inhibitory intralaminar cortical circuits in aged C57Bl/6J mice compared with young adult animals. We speculate that these unbalanced changes in cortical circuits contribute to the functional manifestations of age-related hearing loss.