Response of olfactory axons to loss of synaptic targets in the adult mouse
Response of olfactory axons to loss of synaptic targets in the adult mouse
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DOI：
10.1016/j.expneurol.2007.06.022
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发表时间：
2007-10-01
影响因子：
5.3
通讯作者：
Guthrie, Kathleen
中科院分区：
文献类型：
--
作者：
Ardiles, Yona;de la Puente, Rafael;Guthrie, Kathleen
肾小球会聚被认为依赖于嗅觉轴突之间的相互作用，然而地形靶向受到嗅球中遇到的引导分子的影响。在发育过程中这些线索的破坏会误导感觉轴突，然而我们对球衍生信号在以后生命中的作用知之甚少，因为新的轴突是在嗅觉感觉神经元（OSN）群体更新过程中产生的。为了评估球神经元在维持成人地形投射方面的贡献，我们在 P2-IRES-tauLacZ 小鼠中用 N-甲基-D-天冬氨酸 (NMDA) 消融它们，并检查感觉轴突如何应对突触后伙伴的丧失。 NMDA 损伤消除了球神经元，但不损害感觉轴突或嗅觉鞘神经胶质细胞。病变时肾小球内包含的 P2 轴突在这些位置保持会聚；没有证据表明残余组织有代偿性生长。目标剥夺上皮细胞中 OSN 的延迟凋亡导致 P2 神经元数量下降，以及病变球中 P2 肾小球逐渐萎缩，在某些情况下完全丧失，持续 3 周。上皮细胞增殖的增加部分恢复了 OSN 群，到 8 周时，新的 P2 轴突分布在球残余物和前嗅核内的不同位置。先前的研究表明，嗅觉地形的初始发育并不依赖于与目标神经元的突触形成，然而目前的数据表明，感觉图的持续维护需要存在足够数量和/或类型的可用延髓突触目标。 (C) 2007 Elsevier Inc. 保留所有权利。
Glomerular convergence has been proposed to rely on interactions between like olfactory axons, however topographic targeting is influenced by guidance molecules encountered in the olfactory bulb. Disruption of these cues during development misdirects sensory axons, however little is known about the role of bulb-derived signals in later life, as new axons arise during turnover of the olfactory sensory neuron (OSN) population. To evaluate the contribution of bulb neurons in maintaining topographic projections in adults, we ablated them with N-methyl-D-aspartate (NMDA) in P2-IRES-tauLacZ mice and examined how sensory axons responded to loss of their postsynaptic partners. NMDA lesion eliminated bulb neurons without damage to sensory axons or olfactory ensheathing glia. P2 axons contained within glomeruli at the time of lesion maintained convergence at these locations; there was no evidence of compensatory growth into the remnant tissue. Delayed apoptosis of OSNs in the target-deprived epithelium led to declines in P2 neuron number as well as the gradual atrophy, and in some cases complete loss, of P2 glomeruli in lesioned bulbs by 3 weeks. Increased cell proliferation in the epithelium partially restored the OSN population, and by 8 weeks, new P2 axons distributed within diverse locations in the bulb remnant and within the anterior olfactory nucleus. Prior studies have suggested that initial development of olfactory topography does not rely on synapse formation with target neurons, however the present data demonstrate that continued maintenance of the sensory map requires the presence of sufficient numbers and/or types of available bulbar synaptic targets. (C) 2007 Elsevier Inc. All rights reserved.