Complementary Actions of BDNF and Neurotrophin-3 on the Firing Patterns and Synaptic Composition of Motoneurons
Complementary Actions of BDNF and Neurotrophin-3 on the Firing Patterns and Synaptic Composition of Motoneurons
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DOI：
10.1523/jneurosci.5312-08.2009
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发表时间：
2009-01-14
影响因子：
5.3
通讯作者：
Pastor, Angel M.
中科院分区：
文献类型：
--
作者：
de Carrizosa, Maria A. Davis-Lopez;Morado-Diaz, Camilo J.;Pastor, Angel M.
神经营养因子作为靶源性因子，在发育过程中对神经元的存活至关重要，但在成年期，它们的作用范围扩大，成为突触和形态可塑性的介质。通过轴突切断术的靶点断开产生初始的突触剥离，随后在靶点神经再支配后发生突触重排。我们使用眼外展神经系统的运动神经元作为轴突切断的模型，报告了脑源性神经营养因子（BDNF）、神经营养因子-3（NT-3）或两者的混合物的营养支持，递送到切断的轴突残端，导致在损伤后立即给药时防止突触剥离或一旦发生突触剥离就促进传入神经再支配外展运动神经元，与前庭神经诱发的突触电位的恢复一致。然而，当两种神经营养因子一起应用时，突触营养作用更大。当给予脑源性神经营养因子和NT-3时，轴突切断引起的与眼球运动相关的放电敏感性降低也恢复到正常值，但当仅使用一种神经营养因子时，放电特征以互补的方式恢复。这是第一份报告，显示选择性逆行营养依赖的电路驱动的放电特性在体内表明，NT-3恢复的相位放电，而BDNF支持紧张性放电的运动神经元在眼球运动性能。因此，我们的数据报告之间的联系，神经营养因子的突触营养作用，逆行交付，和运动行为过程中神经元放电模式的改变。这些营养行为可能是负责，部分，突触重排，改变电路的稳定性和突触的平衡，在大脑的可塑性事件。
Neurotrophins, as target-derived factors, are essential for neuronal survival during development, but during adulthood, their scope of actions widens to become also mediators of synaptic and morphological plasticity. Target disconnection by axotomy produces an initial synaptic stripping ensued by synaptic rearrangement upon target reinnervation. Using abducens motoneurons of the oculomotor system as a model for axotomy, we report that trophic support by brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3) or a mixture of both, delivered to the stump of severed axons, results in either the prevention of synaptic stripping when administered immediately after lesion or in a promotion of reinnervation of afferents to abducens motoneurons once synaptic stripping had occurred, in concert with the recovery of synaptic potentials evoked from the vestibular nerve. Synaptotrophic effects, however, were larger when both neurotrophins were applied together. The axotomy-induced reduction in firing sensitivities related to eye movements were also restored to normal values when BDNF and NT-3 were administered, but discharge characteristics recovered in a complementary manner when only one neurotrophin was used. This is the first report to show selective retrograde trophic dependence of circuit-driven firing properties in vivo indicating that NT-3 restored the phasic firing, whereas BDNF supported the tonic firing of motoneurons during eye movement performance. Therefore, our data report a link between the synaptotrophic actions of neurotrophins, retrogradely delivered, and the alterations of neuronal firing patterns during motor behaviors. These trophic actions could be responsible, in part, for synaptic rearrangements that alter circuit stability and synaptic balance during plastic events of the brain.