Russell F A, Moore D R
University Laboratory of Physiology, Oxford, United Kingdom.
J Comp Neurol. 1995 Feb 20;352(4):607-25. doi: 10.1002/cne.903520409.
Cochlear removal in young animals has been shown to produce a variety of degenerative and generative effects within the auditory brainstem. A primary target for axons of neurons in the anteroventral cochlear nucleus (AVCN) is the superior olivary complex (SOC). Following unilateral cochlear removal in neonatal gerbils, AVCN neurons on the side of the removal die, and axons deriving from the AVCN on the unlesioned side produce new endings that innervate previously inappropriate target zones within the ipsilateral medial nucleus of the trapezoid body, both medial superior olives, and the contralateral lateral superior olive. In this study, we have used the anterograde transport of DiI and HRP from the AVCN to relate the formation of these endings to the time course of normal development in the gerbil brainstem. We have also examined the effects of cochlear removal at different ages, and survival to various ages after the removal, to define the time course for these generative phenomena. The results show that, while the major projection pathways from the AVCN to the SOC are in place at the time of birth, further and subtle development of AVCN terminal arbors occurs during the first postnatal week. This overlaps with the time during which cochlear removal produces the formation of exuberant afferents to the SOC from the intact AVCN. The exuberant afferents form through axon sprouting rather than through a suppression of normal, developmental regression. They appear to innervate tonotopically appropriate target regions within the SOC. The formation of the novel afferents begins within 3 days of the removal and appears to be complete within a further 5-7 days. By postnatal day (P) 10, both the normal development of the AVCN to SOC projection and the potential for alteration of that projection by removal of the contralateral cochlea appear to be over. These results suggest that the potential for forming novel projections in the gerbil auditory brainstem is lost before the onset of functional hearing (at P12) and is, therefore, unlikely to result from changes in auditory experience.
幼龄动物的耳蜗切除已被证明会在听觉脑干内产生多种退行性和再生性效应。前腹侧耳蜗核（AVCN）神经元轴突的一个主要靶标是上橄榄复合体（SOC）。新生沙鼠单侧耳蜗切除后，切除侧的AVCN神经元死亡，未受损侧AVCN发出的轴突产生新的终末，支配同侧斜方体内侧核、双侧上橄榄核中先前不适当的靶区。在本研究中，我们利用从AVCN进行的DiI和HRP顺行运输，将这些终末的形成与沙鼠脑干正常发育的时间进程联系起来。我们还研究了不同年龄时耳蜗切除的影响，以及切除后存活到不同年龄的情况，以确定这些再生现象的时间进程。结果表明，虽然出生时从AVCN到SOC的主要投射通路已经形成，但AVCN终末分支在出生后的第一周仍会进一步细微发育。这与耳蜗切除导致完整AVCN向SOC产生丰富传入纤维的时间重叠。丰富的传入纤维通过轴突发芽形成，而不是通过抑制正常的发育性退缩。它们似乎支配SOC内音调定位合适的靶区。新传入纤维的形成在切除后3天内开始，似乎在再过5 - 7天内完成。到出生后第10天，AVCN到SOC投射的正常发育以及对侧耳蜗切除改变该投射的可能性似乎都已结束。这些结果表明，沙鼠听觉脑干中形成新投射的潜力在功能性听力开始（出生后第12天）之前就已丧失，因此不太可能是听觉经验变化的结果。
