Throughout the nervous system, the convergence of two or more presynaptic inputs on a target cell is commonly observed. The question we ask here is to what extent converging inputs influence each other's structural and functional synaptic plasticity. In complex circuits, isolating individual inputs is difficult because postsynaptic cells can receive thousands of inputs. An ideal model to address this question is the Drosophila larval neuromuscular junction (NMJ) where each postsynaptic muscle cell receives inputs from two glutamatergic types of motor neurons (MNs), known as 1b and 1s MNs. Notably, each muscle is unique and receives input from a different combination of 1b and 1s MNs; we surveyed multiple muscles for this reason. Here, we identified a cell-specific promoter that allows ablation of 1s MNs postinnervation and measured structural and functional responses of convergent 1b NMJs using microscopy and electrophysiology. For all muscles examined in both sexes, ablation of 1s MNs resulted in NMJ expansion and increased spontaneous neurotransmitter release at corresponding 1b NMJs. This demonstrates that 1b NMJs can compensate for the loss of convergent 1s MNs. However, only a subset of 1b NMJs showed compensatory evoked neurotransmission, suggesting target-specific plasticity. Silencing 1s MNs led to similar plasticity at 1b NMJs, suggesting that evoked neurotransmission from 1s MNs contributes to 1b synaptic plasticity. Finally, we genetically blocked 1s innervation in male larvae and robust 1b synaptic plasticity was eliminated, raising the possibility that 1s NMJ formation is required to set up a reference for subsequent synaptic perturbations.

SIGNIFICANCE STATEMENT In complex neural circuits, multiple convergent inputs contribute to the activity of the target cell, but whether synaptic plasticity exists among these inputs has not been thoroughly explored. In this study, we examined synaptic plasticity in the structurally and functionally tractable Drosophila larval neuromuscular system. In this convergent circuit, each muscle is innervated by a unique pair of motor neurons. Removal of one neuron after innervation causes the adjacent neuron to increase neuromuscular junction outgrowth and functional output. However, this is not a general feature as each motor neuron differentially compensates. Further, robust compensation requires initial coinnervation by both neurons. Understanding how neurons respond to perturbations in adjacent neurons will provide insight into nervous system plasticity in both healthy and disease states.

在整个神经系统中，通常观察到两个或多个突触前输入在靶细胞上的收敛。我们在这里提出的问题是融合输入在多大程度上影响彼此的结构和功能突触可塑性。在复杂的电路中，隔离单个输入很困难，因为突触后细胞可以接收数千个输入。解决这个问题的理想模型是果蝇幼虫神经肌肉接头 (NMJ)，其中每个突触后肌肉细胞接收来自两种谷氨酸能类型运动神经元 (MN) 的输入，称为 1b 和 1s MN。值得注意的是，每块肌肉都是独一无二的，并且接收来自 1b 和 1s MN 的不同组合的输入；出于这个原因，我们调查了多块肌肉。在这里，我们确定了一种细胞特异性启动子，它允许消融 1s MNs postinnervation 并使用显微镜和电生理学测量会聚 1b NMJs 的结构和功能反应。对于在两性中检查的所有肌肉，1s MNs 的消融导致 NMJ 扩张并增加相应 1b NMJs 处的自发神经递质释放。这表明 1b NMJ 可以补偿收敛的 1s MN 的损失。然而，只有一部分 1b NMJs 表现出代偿性诱发神经传递，暗示目标特定的可塑性。沉默 1s MN 导致 1b NMJ 具有类似的可塑性，这表明 1s MN 诱发的神经传递有助于 1b 突触可塑性。最后，我们在基因上阻断了雄性幼虫的 1s 神经支配，并消除了强大的 1b 突触可塑性，提高了 1s NMJ 形成需要为随后的突触扰动建立参考的可能性。

意义陈述在复杂的神经回路中，多个收敛输入有助于目标细胞的活动，但这些输入之间是否存在突触可塑性尚未得到彻底探索。在这项研究中，我们检查了结构和功能上易于处理的果蝇的突触可塑性幼虫神经肌肉系统。在这个收敛回路中，每块肌肉都由一对独特的运动神经元支配。神经支配后去除一个神经元会导致相邻神经元增加神经肌肉接头的生长和功能输出。然而，这不是一个普遍的特征，因为每个运动神经元都有不同的补偿。此外，稳健的补偿需要两个神经元的初始协同神经。了解神经元如何对相邻神经元的扰动做出反应，将有助于深入了解健康和疾病状态下的神经系统可塑性。