Suneja S K, Potashner S J, Benson C G
Department of Anatomy, University of Connecticut Health Center, Farmington, Connecticut 06030, USA.
Exp Neurol. 2000 Oct;165(2):355-69. doi: 10.1006/exnr.2000.7471.
This study determined if an asymmetric hearing loss, due to unilateral cochlear ablation, could induce the regulation of intracellular AMPA receptors in brain stem auditory nuclei. In young adult guinea pigs, the high-affinity specific binding of [(3)H]AMPA was measured in the cochlear nucleus (CN), the superior olivary complex (SOC), and the auditory midbrain at 2-147 postlesion days. After correction for tissue shrinkage, changes in specific binding relative to that in age-matched unlesioned controls were interpreted as altered numbers and/or activity of intracellular AMPA receptors. In the CN, transient elevations and/or deficits in binding were evident in most regions, which usually recovered by 147 days. However, persistently deficient binding was evident ipsilaterally in the anterior part of the anteroventral CN (AVCNa). In the SOC, transient elevations in binding were evident at 2 days in the medial limb of the lateral superior olive (LSOmed) and the medial superior olive. Between 7 and 147 days, most SOC nuclei exhibited transient, temporally synchronized postlesion deficits in binding. However, late in the survival period, deficits persisted ipsilaterally in the LSOmed and the lateral (LSOlat) limb of the lateral superior olive. In the midbrain, transient elevations and/or deficits in binding were evident in the dorsal nucleus of the lateral lemniscus as well as in the central and dorsal nucleus of the inferior colliculus. A persistent deficit was evident in the intermediate nucleus of the lateral lemniscus. The findings implied that auditory neurons contain regulatory mechanisms that control the numbers and/or activity of intracellular AMPA receptors. Regulation was induced by cochlear nerve destruction and probably by changes in the excitation of glutamatergic neurons. Many of the regulatory changes were transient, except in the ipsilateral AVCNa and LSO, where postlesion downregulations were persistent. The downregulation in the ipsilateral AVCNa was probably induced directly by the loss of cochlear nerve endings. However, other regulatory changes may have been induced by signals carried on pathways emerging from the ipsilateral CN and on centrifugal auditory pathways.
本研究旨在确定单侧耳蜗损毁所致的不对称听力损失是否会诱导脑干听觉核团中细胞内AMPA受体的调节。在成年幼龄豚鼠中，于损伤后2 - 147天测量耳蜗核（CN）、上橄榄复合体（SOC）和听觉中脑中[(3)H]AMPA的高亲和力特异性结合。校正组织收缩后，相对于年龄匹配的未损伤对照，特异性结合的变化被解释为细胞内AMPA受体数量和/或活性的改变。在CN中，大多数区域的结合明显出现短暂升高和/或不足，通常在147天时恢复。然而，在前庭蜗神经核（AVCNa）前部的同侧，结合持续不足。在SOC中，外侧上橄榄核内侧支（LSOmed）和内侧上橄榄核在损伤后2天结合明显短暂升高。在7至147天之间，大多数SOC核团在结合方面表现出短暂的、时间同步的损伤后不足。然而，在存活期后期，LSOmed和外侧上橄榄核外侧支（LSOlat）的同侧仍存在不足。在中脑中，外侧丘系背核以及下丘中央核和背核的结合明显出现短暂升高和/或不足。外侧丘系中间核存在持续不足。这些发现表明，听觉神经元含有控制细胞内AMPA受体数量和/或活性的调节机制。调节是由耳蜗神经破坏诱导的，可能还由谷氨酸能神经元兴奋的变化诱导。除了同侧AVCNa和LSO中损伤后下调持续存在外，许多调节变化是短暂的。同侧AVCNa中的下调可能直接由耳蜗神经末梢的丧失诱导。然而，其他调节变化可能是由同侧CN发出的通路以及离心听觉通路上携带的信号诱导的。
