Wawrzyniak Alexa, Busby Justine, Dalo Alice, Duncan Syllissa, Almassri Laila S, Smallridge Dakota Z, Ohl Andrew P, Mafi Amir M, Tokar Nick J, Young Jesse W, Mellott Jeffrey G
Department of Anatomy and Neurobiology, Northeast Ohio Medical University, Rootstown, OH, USA.
Department of Anatomy and Neurobiology, Northeast Ohio Medical University, Rootstown, OH, USA; University Hospitals Hearing Research Center, Northeast Ohio Medical University, Rootstown, OH, USA.
Neurobiol Aging. 2025 Sep;153:30-48. doi: 10.1016/j.neurobiolaging.2025.06.002. Epub 2025 Jun 6.
Presbycusis, one of the most widespread disorders, is in part associated with the loss of temporal precision within the central auditory system. A contributor to the dysfunctional temporal precision during aging is the substantial downregulation of GABA in the central inferior colliculus (ICc), the hub of ascending and descending inputs of the auditory midbrain. However, how GABAergic inputs across the tonotopic axis of the ICc change with age has not been well explored. We sought to determine age-related changes to GABAergic synapses in the lemniscal ICc, and if changes are uniform across the ICc axis. Using immuno-electron microscopy across four age groups of Fisher Brown Norway rats, a model that acquires low frequency presbycusis, our results demonstrate several nonuniform ultrastructural changes to GABAergic synapses in the ICc. There was a significant (∼29-33 %) downregulation of GABAergic synapses in the high and middle frequency regions of old rats, but a loss (∼22 %) in the old low frequency region was not as robust and did not reach statistical significance. Interestingly, in the high and middle frequency regions, GABAergic presynaptic area increased with age, while there was an ultimately decline in the old low frequency region. Also unique to the high and middle frequencies was the increasing proportion of GABAergic synapses onto larger GABAergic dendrites. These changes demonstrate that aging differentially affects the GABAergic ultrastructure of the ICc tonotopic axis.
老年性聋是最普遍的疾病之一，部分与中枢听觉系统中时间精度的丧失有关。衰老过程中导致时间精度功能失调的一个因素是，听觉中脑上下行输入枢纽——中枢下丘（ICc）中γ-氨基丁酸（GABA）的大量下调。然而，ICc音频定位轴上的GABA能输入如何随年龄变化尚未得到充分研究。我们试图确定lemniscal ICc中GABA能突触与年龄相关的变化，以及这些变化在整个ICc轴上是否一致。通过对四个年龄组的Fisher Brown Norway大鼠（一种会出现低频老年性聋的模型）进行免疫电子显微镜观察，我们的结果显示ICc中GABA能突触存在几种不均匀的超微结构变化。老年大鼠高频和中频区域的GABA能突触显著下调（约29%-33%），但老年低频区域的损失（约22%）不那么明显，未达到统计学意义。有趣的是，在高频和中频区域，GABA能突触前面积随年龄增加，而老年低频区域最终下降。高频和中频区域的独特之处还在于，GABA能突触在较大GABA能树突上的比例增加。这些变化表明，衰老对ICc音频定位轴的GABA能超微结构有不同影响。
