Activity-driven sharpening of the retinotectal projection: the search for retrograde synaptic signaling pathways.

Activity-driven sharpening of the retinotectal projection: the search for retrograde synaptic signaling pathways.
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活动驱动的视网膜顶盖投射锐化:寻找逆行突触信号通路。

DOI:
10.1002/neu.10343
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发表时间:
2004
期刊:
Journal of neurobiology
影响因子:
--
通讯作者:
John T. Schmidt
John T. Schmidt
中科院分区:
--
文献类型:
--
作者:
John T. Schmidt

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图案化的视觉活动通过NMDA受体发挥作用,通过塑造单个视网膜乔木来完善正在形成的视网膜顶盖地图。由于NMDA受体是突触后的,而视网膜的树枝是突触前的,因此必须通过NMDA受体在Ca(++)进入的下游产生逆行信号,引导突触前视网膜终末稳定和生长或退出。该综述定义了逆行突触信使的标准,并将其应用于主要候选者:一氧化氮(NO)、脑源性神经营养因子(BDNF)和花生四烯酸(AA)。NO不太可能是一种通用的机制,因为它只在温血脊椎动物的选定投射中起作用,以加快突触的精细化,但不是必不可少的。BDNF是一种神经营养因子,具有很强的促生长特性,与其释放和受体信号转导活性相互作用复杂,但可能调节而不是介导逆行信号转导。AA通过利用L1、NCAM、N-钙粘蛋白和成纤维细胞生长因子利用的轴突生长促进途径促进突触终末的生长和稳定,并通过PKC、GAP43和F-肌动蛋白稳定作用,它与BDNF途径有一些重叠。两者的行为都与最近的证据一致,即活动驱动的稳定包括新突触接触的定向增长。某些非扩散因子(突触特异性细胞黏附分子、肾上腺素、神经尿素素/神经连接蛋白和基质分子)也可能在活动驱动的突触稳定中发挥作用。讨论了这些途径之间的相互作用。
Patterned visual activity, acting via NMDA receptors, refines developing retinotectal maps by shaping individual retinal arbors. Because NMDA receptors are postsynaptic but the retinal arbors are presynaptic, there must be retrograde signals generated downstream of Ca(++) entry through NMDA receptors that direct the presynaptic retinal terminals to stabilize and grow or to withdraw. This review defines criteria for retrograde synaptic messengers, and then applies them to the leading candidates: nitric oxide (NO), brain-derived neurotrophic factor (BDNF), and arachidonic acid (AA). NO is not likely to be a general mechanism, as it operates only in selected projections of warm blooded vertebrates to speed up synaptic refinement, but is not essential. BDNF is a neurotrophin with strong growth promoting properties and complex interactions with activity both in its release and receptor signaling, but may modulate rather than mediate the retrograde signaling. AA promotes growth and stabilization of synaptic terminals by tapping into a pre-existing axonal growth-promoting pathway that is utilized by L1, NCAM, N-cadherin, and FGF and acts via PKC, GAP43, and F-actin stabilization, and it shares some overlap with BDNF pathways. The actions of both are consistent with recent demonstrations that activity-driven stabilization includes directed growth of new synaptic contacts. Certain nondiffusible factors (synapse-specific CAMs, ephrins, neurexin/neuroligin, and matrix molecules) may also play a role in activity-driven synapse stabilization. Interactions between these pathways are discussed.
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