The 100-y-old neuron doctrine from Ramón y Cajal states that neurons are individual cells, rejecting the process of cell−cell fusion in the normal development and function of the nervous system. However, fusogens—specialized molecules essential and sufficient for the fusion of cells—are expressed in the nervous system of different species under conditions of viral infection, stress, or disease. Despite these findings, whether the expression of fusogens in neurons leads to cell−cell fusion, and, if so, whether this affects neuronal fate, function, and animal behavior, has not been explored. Here, using Caenorhabditis elegans chemosensory neurons as a model system, we provide proof-of-principle that aberrant expression of fusogens in neurons results in neuron−neuron fusion and behavioral impairments. We demonstrate that fusion between chemoattractive neurons does not affect the response to odorants, whereas fusion between chemoattractive and chemorepulsive neurons compromises chemosensation. Moreover, we provide evidence that fused neurons are viable and retain their original specific neuronal fate markers. Finally, analysis of calcium transients reveals that fused neurons become electrically coupled, thereby compromising neural circuit connectivity. Thus, we propose that aberrant expression of fusogens in the nervous system disrupts neuronal individuality, which, in turn, leads to a change in neural circuit connectivity and disruption of normal behavior. Our results expose a previously uncharacterized basis of circuit malfunction, and a possible underlying cause of neurological diseases.

来自拉蒙·卡哈尔（Ramóny Cajal）的具有100年历史的神经元学说指出，神经元是单个细胞，拒绝了神经系统正常发育和功能中的细胞间融合过程。但是，融合蛋白-细胞融合所必需的足够的特殊分子-在病毒感染，压力或疾病的条件下在不同物种的神经系统中表达。尽管有这些发现，融合蛋白在神经元中的表达是否会导致细胞间融合，以及是否会影响神经元的命运，功能和动物行为，还没有得到探讨。在这里，使用秀丽隐杆线虫化学感应神经元作为模型系统，我们提供原理证明，神经元中融合基因的异常表达会导致神经元-神经元融合和行为障碍。我们证明趋化性神经元之间的融合不会影响对气味的反应，而趋化性和化学趋化性神经元之间的融合会损害化学感觉。此外，我们提供证据表明融合的神经元是可行的，并保留了其原始的特定神经元命运标记。最后，对钙瞬变的分析表明，融合的神经元开始电耦合，从而损害了神经回路的连通性。因此，我们提出融合蛋白在神经系统中的异常表达会破坏神经元的个体性，进而导致神经回路连接性的改变和正常行为的破坏。