Activity-Dependent Synaptic Refinement: New Insights from Drosophila.
Activity-Dependent Synaptic Refinement: New Insights from Drosophila.
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DOI：
10.3389/fnsys.2017.00023
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发表时间：
2017
影响因子：
3
通讯作者：
Keshishian H
中科院分区：
文献类型：
--
作者：
Vonhoff F;Keshishian H
在发育过程中，神经元在寻找突触伙伴时会建立不适当的连接，导致多余的突触必须被修剪掉。错配突触的移除通常涉及电活动，通常是通过Hebbian的尖峰计时机制。果蝇使用了一种新的依赖活动的精化形式，它可能是非Hebbian的，对于产生在该系统中观察到的精确连接至关重要。在果蝇中，运动神经元使用谷氨酸和生物胺章鱼胺进行神经传递，肌肉纤维接受多个突触输入。运动神经元生长锥以时间调节的方式对突触后伙伴发出的多种趋化信号做出反应。这一机制的核心是突触前胞浆钙离子的极低频率(0.03赫兹)振荡，它调节和协调参与退出靶外接触的多个下游效应器的行动。低频钙振荡广泛存在于哺乳动物神经回路的发育中，对多种神经系统的正常连接起着至关重要的作用。在果蝇中，这些机制允许生长锥在可能的突触伙伴中广泛采样，评估对手的趋化信号，并退出靶外接触。潜在的分子机制可能在无脊椎动物和脊椎动物中广泛保守。
During development, neurons establish inappropriate connections as they seek out their synaptic partners, resulting in supernumerary synapses that must be pruned away. The removal of miswired synapses usually involves electrical activity, often through a Hebbian spike-timing mechanism. A novel form of activity-dependent refinement is used by Drosophila that may be non-Hebbian, and is critical for generating the precise connectivity observed in that system. In Drosophila, motoneurons use both glutamate and the biogenic amine octopamine for neurotransmission, and the muscle fibers receive multiple synaptic inputs. Motoneuron growth cones respond in a time-regulated fashion to multiple chemotropic signals arising from their postsynaptic partners. Central to this mechanism is a very low frequency (<0.03 Hz) oscillation of presynaptic cytoplasmic calcium, that regulates and coordinates the action of multiple downstream effectors involved in the withdrawal from off-target contacts. Low frequency calcium oscillations are widely observed in developing neural circuits in mammals, and have been shown to be critical for normal connectivity in a variety of neural systems. In Drosophila these mechanisms allow the growth cone to sample widely among possible synaptic partners, evaluate opponent chemotropic signals, and withdraw from off-target contacts. It is possible that the underlying molecular mechanisms are conserved widely among invertebrates and vertebrates.