Neuropeptide-Driven Cross-Modal Plasticity following Sensory Loss in Caenorhabditis elegans.
Neuropeptide-Driven Cross-Modal Plasticity following Sensory Loss in Caenorhabditis elegans.
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DOI：
10.1371/journal.pbio.1002348
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发表时间：
2016-01
期刊：
影响因子：
9.8
通讯作者：
Treinin M
中科院分区：
文献类型：
--
作者：
Rabinowitch I;Laurent P;Zhao B;Walker D;Beets I;Schoofs L;Bai J;Schafer WR;Treinin M
感觉丧失会引起跨模态可塑性，通常会导致其余感觉模态的表现改变。尽管人们对跨模态塑性的宏观机制了解很多，但关于其细胞和分子基础的信息却很少。我们发现，秀丽隐杆线虫被剥夺了身体触觉的感觉，表现出各种行为的变化，与其他未受损的感官。我们专注于这样一个行为改变，增强气味感觉，并试图揭示神经元和分子机制，翻译机械感觉损失改善嗅觉敏锐度。为此，我们分析了机械感觉突变体的食物依赖的运动模式，与嗅觉反应，并发现变化是一致的增强嗅觉。在成年人中，通过光遗传学刺激触觉感受器（机械感觉）神经元，可以逆转改变的运动。此外，我们发现，气味反应的增强与嗅觉回路中抑制性AWC→AIY突触传递的加强有关。因此，在这个回路中插入一个工程化的电突触，减少AWC抑制AIY抵消了触摸缺陷突变体的运动变化。我们发现，这种机械感觉和嗅觉回路之间的跨模态信号是由神经肽介导的，其中之一我们确定为FLP-20。我们的研究结果表明，在正常功能下，持续的触觉感受器神经元激活引起FLP-20的释放，抑制突触通信，从而抑制气味感觉。相反，在没有机械感觉输入的情况下，FLP-20信号传导减少，突触抑制被释放，这使得嗅觉敏锐度增强;这些变化是持久的，并不代表正在进行的调节，如光遗传学实验所揭示的。我们的工作增加了越来越多的文献中的神经肽在跨模态信号传导的作用，通过显示活动依赖性神经肽信号传导如何导致特定的跨模态可塑性变化的神经回路连接，增强感觉性能。秀丽隐杆线虫的触觉感受神经元通过嗅觉回路中的特定突触分泌神经肽来抑制嗅觉。失去触觉会释放这种抑制，增强嗅觉。大脑具有非凡的能力，通过增强剩余的功能感官来应对感官丧失。例如，盲人的某些听力特征得到改善。这种效应背后的细胞和分子机制是什么？某种感觉是如何加强的？如果有可能听得更好，为什么我们不首先听得更好？为了简化这些问题，我们在一种神经系统远比人类简单的生物体--蛔虫C身上进行了研究。优雅我们发现C.不能感觉身体接触的线虫突变体表现出改善的嗅觉。我们能够将这种感觉表现的变化精确地定位为嗅觉回路中特定突触强度的变化。我们进一步发现，在正常蠕虫中，这种嗅觉突触通过从触觉神经元传递的神经肽信号被抑制。相比之下，在没有任何触摸输入的情况下，触摸神经元分泌的神经肽较少，嗅觉突触变得更强，嗅觉得到改善。我们能够通过人工刺激触觉神经元和在嗅觉回路中设计一个新的突触来逆转这些影响。
Sensory loss induces cross-modal plasticity, often resulting in altered performance in remaining sensory modalities. Whereas much is known about the macroscopic mechanisms underlying cross-modal plasticity, only scant information exists about its cellular and molecular underpinnings. We found that Caenorhabditis elegans nematodes deprived of a sense of body touch exhibit various changes in behavior, associated with other unimpaired senses. We focused on one such behavioral alteration, enhanced odor sensation, and sought to reveal the neuronal and molecular mechanisms that translate mechanosensory loss into improved olfactory acuity. To this end, we analyzed in mechanosensory mutants food-dependent locomotion patterns that are associated with olfactory responses and found changes that are consistent with enhanced olfaction. The altered locomotion could be reversed in adults by optogenetic stimulation of the touch receptor (mechanosensory) neurons. Furthermore, we revealed that the enhanced odor response is related to a strengthening of inhibitory AWC→AIY synaptic transmission in the olfactory circuit. Consistently, inserting in this circuit an engineered electrical synapse that diminishes AWC inhibition of AIY counteracted the locomotion changes in touch-deficient mutants. We found that this cross-modal signaling between the mechanosensory and olfactory circuits is mediated by neuropeptides, one of which we identified as FLP-20. Our results indicate that under normal function, ongoing touch receptor neuron activation evokes FLP-20 release, suppressing synaptic communication and thus dampening odor sensation. In contrast, in the absence of mechanosensory input, FLP-20 signaling is reduced, synaptic suppression is released, and this enables enhanced olfactory acuity; these changes are long lasting and do not represent ongoing modulation, as revealed by optogenetic experiments. Our work adds to a growing literature on the roles of neuropeptides in cross-modal signaling, by showing how activity-dependent neuropeptide signaling leads to specific cross-modal plastic changes in neural circuit connectivity, enhancing sensory performance. Touch-sensing neurons in the nematode Caenorhabditis elegans secrete neuropeptides to suppress olfaction via a specific synapse in the olfactory circuit. Loss of touch releases this suppression, enhancing the sense of smell. The brain has the remarkable capacity to respond to sensory loss by boosting remaining functioning senses. For example, certain features of hearing are improved in blind people. What are the cellular and molecular mechanisms underlying this effect? How is a certain sense strengthened? If it is possible to hear better, why don’t we hear better in the first place? To simplify these problems, we examined them in an organism with a substantially less complicated nervous system than our own, the roundworm C. elegans. We discovered that C. elegans mutants that cannot sense touch to the body exhibit an improved sense of smell. We were able to pinpoint this change in sensory performance to a change in strength of a specific synapse in the olfactory circuit. We further found that in normal worms, this olfactory synapse is suppressed through a neuropeptide signal transmitted from the touch sensing neurons. In contrast, without any touch input, the touch neurons secrete less neuropeptide, the olfactory synapse becomes stronger, and the sense of smell improves. We were able to reverse these effects by artificially stimulating the touch neurons and by engineering a new synapse into the olfactory circuit.