Meidinger Markus A, Hildebrandt-Schoenfeld Heika, Illing Robert-Benjamin
Neurobiological Research Laboratory, Department of Otorhinolaryngology, University of Freiburg, D-79106 Freiburg, Germany.
Eur J Neurosci. 2006 Jun;23(12):3187-99. doi: 10.1111/j.1460-9568.2006.04853.x.
Recent studies suggest a potential for activity-dependent reconstruction in the adult mammalian brainstem that exceeds previous expectations. We found that a unilateral cochlear lesion led within 1 week to a rise of choline acetyltransferase (ChAT) immunoreactivity in the ventral cochlear nucleus of the affected side, matching the lesion-induced expression of growth-associated protein 43 (GAP-43) previously described. The rise of both ChAT and GAP-43 immunoreactivity was reflected in the average density of the staining. Moreover, the number of light-microscopically identifiable boutons increased in both stains. GAP-43-positive boutons could, by distinct ultrastructural features, regularly be identified as presynaptic endings. However, GAP-43 immunoreactivity was not only found in presynaptic endings with a classical morphology, but also in profiles that suggest morphological dynamic structures by showing filopodia, assemblages of pleomorphic vesicles, large vesicles (diameter up to 200 nm) fusing with the presynaptic plasma membrane close to synaptic contacts, small dense-core vesicles (diameter about 80 nm) and presynaptic ribosomes. Moreover, we observed perforated synapses as well as GAP-43 immunoreactivity condensed in rafts, both indicative of growing or changing neuronal connections. Classical and untypical ultrastructural profiles that contained GAP-43 also contained ChAT. We conclude that there is extensive deafness-induced GAP-43-mediated synaptic plasticity in the cochlear nucleus, and that this plasticity is predominantly, if not exclusively, based on cholinergic afferents.
最近的研究表明，成年哺乳动物脑干中存在与活动相关的重建潜力，这超出了先前的预期。我们发现，单侧耳蜗损伤在1周内导致患侧腹侧耳蜗核中胆碱乙酰转移酶（ChAT）免疫反应性升高，与先前描述的损伤诱导的生长相关蛋白43（GAP-43）表达相匹配。ChAT和GAP-43免疫反应性的升高反映在染色的平均密度上。此外，两种染色中光学显微镜下可识别的终扣数量均增加。通过独特的超微结构特征，GAP-43阳性终扣可被常规鉴定为突触前末梢。然而，GAP-43免疫反应性不仅存在于具有经典形态的突触前末梢中，还存在于通过丝状伪足、多形性囊泡集合、靠近突触接触处与突触前质膜融合的大囊泡（直径达200nm）、小致密核心囊泡（直径约80nm）和突触前核糖体显示出形态动态结构的轮廓中。此外，我们观察到穿孔突触以及GAP-43免疫反应性在筏中浓缩，这两者都表明神经元连接在生长或变化。包含GAP-43的经典和非典型超微结构轮廓也包含ChAT。我们得出结论，耳蜗核中存在广泛的耳聋诱导的GAP-43介导的突触可塑性，并且这种可塑性主要（如果不是唯一）基于胆碱能传入神经。
