Physiologic and Nanoscale Distinctions Define Glutamatergic Synapses in Tonic vs Phasic Neurons
Physiologic and Nanoscale Distinctions Define Glutamatergic Synapses in Tonic vs Phasic Neurons
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DOI：
10.1523/jneurosci.0046-23.2023
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发表时间：
2023-06-21
影响因子：
5.3
通讯作者：
Dickman, Dion
中科院分区：
文献类型：
--
作者：
He, Kaikai;Han, Yifu;Dickman, Dion
神经元表现出惊人的功能多样性，每一个神经元都根据其所嵌入的回路的需要进行调整。一种基本的功能二分法出现在活动模式中，一些神经元以相对恒定的“强直”速率放电，而另一些神经元以爆发的方式放电，这是一种“阶段性”模式。由强直和相相神经元形成的突触在功能上也有区别，但其独特特性的基础仍然是谜。阐明强直神经元和相位神经元之间突触差异的一个主要挑战是很难分离出它们的生理特性。在果蝇神经肌肉连接处，大多数肌纤维由两个运动神经元共同支配：强直性“MN-Ib”和相性“MN-Is”。在这里，我们使用选择性表达一种新开发的肉毒杆菌神经毒素转基因来沉默果蝇幼虫的强直性或阶段性运动神经元。这种方法强调了它们的神经递质释放特性的主要差异，包括概率、短期可塑性和囊泡池。此外，Ca2+成像表明；2倍多的Ca2+内流在阶段性神经元释放位点相对于tonic，随着突触囊泡偶联增强。最后，共聚焦和超分辨率成像显示，相对于其他活性区支架折叠，相控型Ca2+通道的化学计量学增强，相控型神经元释放位点的组织结构更加紧凑。这些数据表明，活性区纳米结构和Ca2+内流的差异协同作用，在强直与相位突触亚型中不同地调节谷氨酸释放。
Neurons exhibit a striking degree of functional diversity, each one tuned to the needs of the circuitry in which it is embedded. A fun-damental functional dichotomy occurs in activity patterns, with some neurons firing at a relatively constant "tonic" rate, while others fire in bursts, a "phasic" pattern. Synapses formed by tonic versus phasic neurons are also functionally differentiated, yet the bases of their distinctive properties remain enigmatic. A major challenge toward illuminating the synaptic differences between tonic and phasic neurons is the difficulty in isolating their physiological properties. At the Drosophila neuromuscular junction, most muscle fibers are coinnervated by two motor neurons: the tonic "MN-Ib" and phasic "MN-Is." Here, we used selective expression of a newly developed botulinum neurotoxin transgene to silence tonic or phasic motor neurons in Drosophila larvae of either sex. This approach highlighted major differences in their neurotransmitter release properties, including probability, short-term plasticity, and vesicle pools. Furthermore, Ca2+ imaging demonstrated ;2-fold greater Ca2+ influx at phasic neuron release sites relative to tonic, along with an enhanced synaptic vesicle coupling. Finally, confocal and super-resolution imaging revealed that phasic neuron release sites are organ-ized in a more compact arrangement, with enhanced stoichiometry of voltage-gated Ca2+ channels relative to other active zone scaf-folds. These data suggest that distinctions in active zone nano-architecture and Ca2+ influx collaborate to differentially tune glutamate release at tonic versus phasic synaptic subtypes.