Circumventing neural damage in a C. elegans chemosensory circuit using genetically engineered synapses.
Circumventing neural damage in a C. elegans chemosensory circuit using genetically engineered synapses.
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DOI：
10.1016/j.cels.2020.12.003
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发表时间：
2021-03-17
期刊：
影响因子：
9.3
通讯作者：
Bai J
中科院分区：
文献类型：
--
作者：
Rabinowitch I;Upadhyaya B;Pant A;Galski D;Kreines L;Bai J
神经元的损失可以大大降低神经回路的功能，通过破坏回路中的信息流来损害正常行为。在这里，我们使用基因工程的电突触来重新路由C中的信息流。elegans破坏化学感受回路，以恢复机体行为。我们通过从回路中移除一对中间神经元来削弱趋化性，然后通过在它们中异位表达间隙差距连接蛋白来人工偶联另外两个相邻的神经元对。这恢复了动物的趋化性。我们期望在恢复的回路中观察到连接蛋白偶联神经元之间的线性和直接信息流，但也揭示了连接蛋白表达神经元对内新的有效的左右侧电连接的形成。我们的分析表明，这些额外的电突触除了模仿野生型回路外，还通过放大受损回路中减弱的神经元信号来帮助恢复回路功能。本文的透明同行评审过程的记录包含在补充信息中。由于损伤或疾病导致的神经元损失可能导致相当大的损伤。我们想知道是否可以通过在受损的神经回路中插入新的突触连接来缓解这种情况，为信息流提供替代途径。我们集中研究了微小线虫C.优雅在这个回路中，一对中间神经元的损失会降低化学感受性能。我们设计了一个突触旁路，通过基因插入电突触到电路中来实现，它恢复了行为表现。我们进一步发现，合成连接的影响也是由于受损回路中减弱的感觉信号的放大，这是由于新的横向左右电连接的形成。我们的研究结果表明，工程电突触作为一种工具，用于分析神经回路的结构-功能关系，并作为一个潜在的策略，修复受损的神经回路的力量。
Neuronal loss can considerably diminish neural circuit function, impairing normal behavior by disrupting information flow in the circuit. Here, we use genetically engineered electrical synapses to reroute the flow of information in a C. elegans damaged chemosensory circuit, in order to restore organism behavior. We impaired chemotaxis by removing one pair of interneurons from the circuit, then artificially coupled two other adjacent neuron pairs through ectopically expressing in them the gap junction protein connexin. This restored chemotaxis in the animals. We expected to observe linear and direct information flow between the connexin-coupled neurons in the recovered circuit, but also revealed a formation of new potent left-right lateral electrical connections within the connexin-expressing neuron pairs. Our analysis suggests that these additional electrical synapses help restore circuit function by amplifying weakened neuronal signals in the damaged circuit, in addition to emulating the wild-type circuit. A record of this paper’s Transparent Peer Review process is included in the Supplemental Information. Neuronal loss due to injury or disease could lead to considerable impairments. We asked whether such conditions could be alleviated by genetically inserting new synaptic connections into the damaged neural circuit, providing alternative pathways for information flow. We focused on the relatively simple and extensively studied olfactory circuit of the tiny nematode worm, C. elegans. Loss of a single pair of interneurons in this circuit diminished chemosensory performance. We designed a synaptic bypass, implemented by genetically inserting an electrical synapse into the circuit, which restored behavioral performance. We further found that the impact of the synthetic connection was due also to the amplification of weakened sensory signals in the damaged circuit, enabled by the formation of new lateral left-right electrical connections. Our findings demonstrate the power of engineered electrical synapses as a tool for analyzing neural circuit structure-function relations and as a potential strategy for the repair of damaged neural circuits.
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