The Picower Institute for Learning and Memory, Department of Biology and Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139.
The Picower Institute for Learning and Memory, Department of Biology and Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139
J Neurosci. 2020 Aug 12;40(33):6270-6288. doi: 10.1523/JNEUROSCI.0925-20.2020. Epub 2020 Jul 6.
Structural and functional plasticity induced by neuronal competition is a common feature of developing nervous systems. However, the rules governing how postsynaptic cells differentiate between presynaptic inputs are unclear. In this study, we characterized synaptic interactions following manipulations of tonic Ib or phasic Is glutamatergic motoneurons that coinnervate postsynaptic muscles of male or female larvae. After identifying drivers for each neuronal subtype, we performed ablation or genetic manipulations to alter neuronal activity and examined the effects on synaptic innervation and function at neuromuscular junctions. Ablation of either Ib or Is resulted in decreased muscle response, with some functional compensation occurring in the Ib input when Is was missing. In contrast, the Is terminal failed to show functional or structural changes following loss of the coinnervating Ib input. Decreasing the activity of the Ib or Is neuron with tetanus toxin light chain resulted in structural changes in muscle innervation. Decreased Ib activity resulted in reduced active zone (AZ) number and decreased postsynaptic subsynaptic reticulum volume, with the emergence of filopodial-like protrusions from synaptic boutons of the Ib input. Decreased Is activity did not induce structural changes at its own synapses, but the coinnervating Ib motoneuron increased the number of synaptic boutons and AZs it formed. These findings indicate that tonic Ib and phasic Is motoneurons respond independently to changes in activity, with either functional or structural alterations in the Ib neuron occurring following ablation or reduced activity of the coinnervating Is input, respectively. Both invertebrate and vertebrate nervous systems display synaptic plasticity in response to behavioral experiences, indicating that underlying mechanisms emerged early in evolution. How specific neuronal classes innervating the same postsynaptic target display distinct types of plasticity is unclear. Here, we examined whether tonic Ib and phasic Is motoneurons display competitive or cooperative interactions during innervation of the same muscle, or compensatory changes when the output of one motoneuron is altered. We established a system to differentially manipulate the motoneurons and examined the effects of cell type-specific changes to one of the inputs. Our findings indicate Ib and Is motoneurons respond differently to activity mismatch or loss of the coinnervating input, with the Ib subclass responding robustly compared with Is motoneurons.
神经元竞争诱导的结构和功能可塑性是发育中神经系统的共同特征。然而，支配突触后细胞如何区分突触前输入的规则尚不清楚。在这项研究中，我们描述了 tonic Ib 或 phasic Is 谷氨酸能运动神经元的突触相互作用，这些神经元共同支配雄性或雌性幼虫的突触后肌肉。在确定了每个神经元亚型的驱动因素后，我们进行了消融或遗传操作以改变神经元活动，并检查了对神经肌肉接头突触传入和功能的影响。Ib 或 Is 的消融导致肌肉反应减弱，当 Is 缺失时，Ib 输入出现一些功能补偿。相比之下，当共同支配的 Ib 输入缺失时，Is 末梢没有表现出功能或结构变化。使用破伤风毒素轻链降低 Ib 或 Is 神经元的活性会导致肌肉支配的结构变化。Ib 活性的降低导致活性区（AZ）数量减少和突触后亚突触质体积减少，Ib 输入的突触小泡出现丝状样突起。Is 活性的降低不会在其自身突触处引起结构变化，但共同支配的 Ib 运动神经元增加了它形成的突触小泡和 AZ 的数量。这些发现表明，tonic Ib 和 phasic Is 运动神经元对活性变化的反应是独立的，Ib 神经元在消融或共同支配的 Is 输入活性降低后会发生功能或结构改变，而 coinnervating Ib 神经元会增加其形成的突触小泡和 AZ 的数量。这些发现表明，无论是在无脊椎动物还是脊椎动物神经系统中，都会对行为经验产生突触可塑性，这表明这种机制在进化早期就出现了。支配相同突触后靶标的特定神经元类如何表现出不同类型的可塑性尚不清楚。在这里，我们研究了在同一肌肉的支配过程中，tonic Ib 和 phasic Is 运动神经元是否表现出竞争或合作相互作用，或者当一个运动神经元的输出发生改变时是否表现出代偿性变化。我们建立了一个系统来对运动神经元进行差异操作，并研究了对一个输入进行细胞类型特异性改变的影响。我们的发现表明，Ib 和 Is 运动神经元对活动不匹配或共同支配输入的丢失有不同的反应，与 Is 运动神经元相比，Ib 亚类的反应更强烈。
