Department of Biology, University of Maryland, College Park, MD 20742, United States.
Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD 21205, United States; Department of Biology, University of Maryland, College Park, MD 20742, United States.
Hear Res. 2023 Mar 1;429:108685. doi: 10.1016/j.heares.2022.108685. Epub 2022 Dec 27.
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.
衰老的一个常见障碍是与年龄相关的听力损失（老年性聋），其表现为频谱时间处理受损。衰老伴随着正常抑制性（GABA）神经递质传递的改变，以及听觉皮层（ACtx）中兴奋性（NMDA 和 AMPA）突触的变化。然而，这些突触变化影响的回路仍不清楚。C57Bl/6J 品系的小鼠表现出与年龄相关的听力损失过早和 ACtx 中功能反应的变化。因此，我们通过比较年轻（约 6 周）和年老（>1 岁）的 C57Bl/6J 小鼠，研究了听觉皮层微电路如何随年龄变化。我们对年轻成年和年老 C57Bl/6J 小鼠初级听觉皮层（A1）的 L2/3 细胞进行了激光扫描光刺激（LSPS）与全细胞膜片钳记录相结合的实验。我们发现，年老 C57Bl/6J 小鼠的 L2/3 细胞显示兴奋性和抑制性回路的功能连接不足。与来自年轻 C57Bl/6 小鼠的细胞相比，来自年老 C57Bl/6J 小鼠的细胞具有更少的兴奋性连接，并且连接强度较弱。尽管年轻成年和年老 C57Bl/6J 小鼠具有相似数量的抑制性连接，但老年组的局部抑制强度较弱。通过记录微小兴奋性（mEPSC）和抑制性突触电流（mIPSC），我们证实了这些结果。我们的结果表明，与年轻成年动物相比，年老 C57Bl/6J 小鼠的皮层内层兴奋性和抑制性回路有特定的减少。我们推测，这些皮层回路的不平衡变化导致了与年龄相关的听力损失的功能表现。
