利用”机器视觉技术”研究秀丽线虫抉择的分子机制与神经环路

Decision-making is critical for the survival and evolution of an organism. The fundamental features of decision-making are common to many species and this basic function for choice has remained essentially unchanged. The process of decision is affected by the development of brain regions, learning and memory as well as the sensory perception of surroundings. The individual decision-making is also affected by the group decision in a society or group. However, the underlying mechanisms of individual and group decision-making are not well understood. To derive the rule of decision-making and detailed computational models by revealing the the process by which those choices are generated individually or in a group will provide a new framework for thinking about decision-making and lead to more breakthrough findings. C. elegans has the completely mapped neural connectome and complex behaviors, which make it a powerful model for the investigations of neural mechanisms of sensory integration and decision-making. We establish it as a model for studying the group decisions about food and provide a new tool called “computer vision technology” for investigating and modeling behavior as well as for the study of mechanisms in C. elegans decision-making. Our previous studies show that worms choose a Cost-effective strategy in group decision-making. Our studies lay the foundation for future work which elucidates the molecular mechanisms and the neural circuits underlying decision-making in C. elegans by using a highly integrative approach including molecular genetics, functional calcium imaging, and optogenetic manipulations, and may advance our understanding of decision-making in higher organisms.

抉择对于生物的生存与进化至关重要，其基本特征在物种间保持一致。大脑结构发育及学习记忆均会影响抉择行为；在社会或群体中个体抉择也受外界信息及群体抉择的影响。由于抉择神经活动的复杂性及针对抉择过程和群体行为研究技术的局限性，个体及群体抉择的分子神经机制仍不清楚。聚焦抉择产生的过程及群体的影响，开发相关技术，能为抉择研究提供崭新的视角。秀丽线虫具有简洁清晰的神经图谱和丰富的行为表型，是研究抉择分子神经机制的优良模式动物。我们自主研发了“机器视觉技术”，打破了研究抉择过程及群体行为的技术瓶颈，将其成功运用于线虫群体觅食抉择过程的研究。我们前期结果表明线虫在群体抉择过程中展现了经济高效的抉择策略。本项目将利用线虫的遗传优势与机器视觉，光遗传和功能钙成像等高度综合手段，研究线虫抉择的分子机制和神经环路，探索抉择普适的行为规律与计算原则，为理解高等动物的抉择行为与神经机制提供重要线索。

我们利用秀丽线虫的强大的遗传学优势和清晰的神经图谱，大规模筛选参与调节抉择行为的各种遗传与表观遗传基因。结合多种研究手段包括分子遗传学、成像技术、行为学及新的单细胞测序技术研究了其中的人类同源基因，鉴定了新的参与抉择相关的重要遗传与表观遗传基因。深入地研究了抉择的分子机制、调控网络与相关神经元。找到对应的阻断秀丽线虫学习记忆的表观遗传阻断剂，未来将作为潜在的药物用于学习记忆与抉择的研究。