Ophthalmology, Visual and Anatomical Sciences, School of Medicine, Wayne State University, Detroit, MI 48201, United States of America.
Ophthalmology, Visual and Anatomical Sciences, School of Medicine, Wayne State University, Detroit, MI 48201, United States of America.
Hear Res. 2024 Oct;452:109106. doi: 10.1016/j.heares.2024.109106. Epub 2024 Aug 21.
Several studies suggest that hearing loss results in changes in the balance between inhibition and excitation in the inferior colliculus (IC). The IC is an integral nucleus within the auditory brainstem. The majority of ascending pathways from the lateral lemniscus (LL), superior olivary complex (SOC), and cochlear nucleus (CN) synapse in the IC before projecting to the thalamus and cortex. Many of these ascending projections provide inhibitory innervation to neurons within the IC. However, the nature and the distribution of this inhibitory input have only been partially elucidated in the rat. The inhibitory neurotransmitter, gamma aminobutyric acid (GABA), from the ventral nucleus of the lateral lemniscus (VNLL), provides the primary inhibitory input to the IC of the rat with GABA from other lemniscal and SOC nuclei providing lesser, but prominent innervation. There is evidence that hearing related conditions can result in dysfunction of IC neurons. These changes may be mediated in part by changes in GABA inputs to IC neurons. We have previously used gene micro-arrays in a study of deafness-related changes in gene expression in the IC and found significant changes in GAD as well as the GABA transporters and GABA receptors (Holt 2005). This is consistent with reports of age and trauma related changes in GABA (Bledsoe et al., 1995; Mossop et al., 2000; Salvi et al., 2000). Ototoxic lesions of the cochlea produced a permanent threshold shift. The number, intensity, and density of GABA positive axon terminals in the IC were compared in normal hearing and deafened rats. While the number of GABA immunolabeled puncta was only minimally different between groups, the intensity of labeling was significantly reduced. The ultrastructural localization and distribution of labeling was also examined. In deafened animals, the number of immuno gold particles was reduced by 78 % in axodendritic and 82 % in axosomatic GABAergic puncta. The affected puncta were primarily associated with small IC neurons. These results suggest that reduced inhibition to IC neurons contribute to the increased neuronal excitability observed in the IC following noise or drug induced hearing loss. Whether these deafness diminished inhibitory inputs originate from intrinsic or extrinsic CNIC sources awaits further study.
几项研究表明，听力损失会导致下丘脑中（IC）抑制与兴奋之间的平衡发生变化。IC 是听觉脑干的一个重要核团。来自外侧丘系（LL）、上橄榄核复合体（SOC）和耳蜗核（CN）的大多数上行通路在投射到丘脑和皮质之前在 IC 中突触。其中许多上行投射为 IC 内的神经元提供抑制性神经支配。然而，这种抑制性输入的性质和分布在大鼠中仅部分阐明。来自外侧丘系腹核（VNLL）的抑制性神经递质γ-氨基丁酸（GABA）为大鼠 IC 提供主要的抑制性输入，来自其他丘系和 SOC 核的 GABA 提供较少但明显的神经支配。有证据表明，与听力相关的条件会导致 IC 神经元功能障碍。这些变化可能部分由 IC 神经元 GABA 输入的变化介导。我们之前在一项关于 IC 中与听力相关的基因表达变化的研究中使用了基因微阵列，发现 GAD 以及 GABA 转运体和 GABA 受体有显著变化（Holt 2005）。这与 GABA 与年龄和创伤相关变化的报告一致（Bledsoe 等人，1995；Mossop 等人，2000；Salvi 等人，2000）。耳蜗的耳毒性病变产生永久性阈值移位。在正常听力和耳聋大鼠中比较了 IC 中 GABA 阳性轴突末梢的数量、强度和密度。虽然两组之间 GABA 免疫标记点的数量仅略有差异，但标记强度显著降低。还检查了标记的超微结构定位和分布。在耳聋动物中，轴突树突和轴突体 GABA 能棘突中的免疫金颗粒数量分别减少了 78%和 82%。受影响的棘突主要与小 IC 神经元有关。这些结果表明，IC 神经元的抑制减少导致噪声或药物诱导听力损失后 IC 中观察到的神经元兴奋性增加。这些听力丧失减弱的抑制性输入是否源自内在或外在 CNIC 来源，还需要进一步研究。
