Parks T N
Dept of Neurobiology & Anatomy, University of Utah School of Medicine, Salt Lake City 84132, USA.
Ann Otol Rhinol Laryngol Suppl. 1997 May;168:37-43.
Early destruction of the otocyst (embryonic precursor of the inner ear) in chick embryos results in complex changes in developing central auditory pathways. In the cochlear nucleus angularis (NA) and nucleus magnocellularis (NM), 30% to 40% of the neurons die after otocyst removal, the survivors are shrunken, and some neurons in the NA migrate to an abnormal position in the brain stem. The characteristic forms of cochlear nucleus neurons develop normally in the absence of cochlear nerve input, however. In the nucleus laminaris (NL), development of normal dendritic size is dependent on a normal inner ear, but most of the highly specialized dendritic organization of this nucleus, which is important for low-frequency sound localization, can develop normally in the absence of cochlear influences. Otocyst removal induces formation of a permanent functional aberrant axonal projection to the ipsilateral NM from the contralateral NM. Although these aberrant axons form functional glutamatergic synapses, these show immature functional properties, suggesting that cochlear nerve inputs are necessary for normal maturation of glutamate receptors on auditory neurons. Treatment of chick embryo for a brief period in ovo with 6-cyano-7-nitroquinoxaline-2,3-dione, a quinoxalinedione antagonist of the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate-kainate subtype of glutamate receptor, completely and permanently prevents the neuronal loss in the NM produced by otocyst removal. The work reviewed has 1) identified aspects of development in central auditory neurons that are perturbed by profound early sensorineural loss, 2) identified aspects of development that appear independent of cochlear influences, and 3) suggested a potential chemotherapeutic approach to prevention of central neuronal death after early damage to the cochlea.
鸡胚内耳囊（内耳的胚胎前体）的早期破坏会导致发育中的中枢听觉通路发生复杂变化。在耳蜗角核（NA）和大细胞神经核（NM）中，去除内耳囊后30%至40%的神经元死亡，存活的神经元会萎缩，并且NA中的一些神经元会迁移到脑干中的异常位置。然而，在没有耳蜗神经输入的情况下，耳蜗核神经元的特征性形态仍能正常发育。在层状核（NL）中，正常树突大小的发育依赖于正常的内耳，但该核中大部分高度特化的树突组织（对低频声音定位很重要）在没有耳蜗影响的情况下仍能正常发育。去除内耳囊会诱导从对侧NM向同侧NM形成永久性的功能性异常轴突投射。尽管这些异常轴突形成了功能性谷氨酸能突触，但这些突触显示出不成熟的功能特性，这表明耳蜗神经输入对于听觉神经元上谷氨酸受体的正常成熟是必要的。用6-氰基-7-硝基喹喔啉-2,3-二酮（一种谷氨酸受体α-氨基-3-羟基-5-甲基-4-异恶唑丙酸-海人藻酸亚型的喹喔啉二酮拮抗剂）在鸡胚孵化期进行短时间处理，可完全且永久性地防止因去除内耳囊而导致的NM中的神经元损失。所综述的这项研究1）确定了中枢听觉神经元发育中受早期严重感觉神经性听力损失干扰的方面，2）确定了似乎独立于耳蜗影响的发育方面，3）提出了一种潜在的化学治疗方法，用于预防耳蜗早期损伤后中枢神经元的死亡。
