秀丽线虫情感和记忆神经环路的全光学解析

Modulated by internal emotional states and guided by learning and memory, animal behaviors exhibit high flexibility and plasticity. Such self-adaptation in a changing environment is critical for the survival and multiplication of an animal. To investigate the neural mechanisms underlying behavioral plasticity, we propose to use C. elegans as a model system to dissect the neural circuit underlying behavioral plasticity by integrating behavior, genetics, and optical neurophysiology. In previous work, we have discovered that C. elegans show reliable learning and memory abilities when exposed to temperature and chemical stimuli. Driven by a distributed neural network, worms exhibit flexible thermotactic and chemotactic behaviors. Moreover, studies have shown that serotonin, a biogenic amine that plays critical roles in mediating aversive emotions in human, can also effectively modulate learning and memory in C. elegans. Next, we will first use "whole brain" calcium imaging technique and optogenetic method to monitor and manipulate all neurons underlying a defined sensorimotor behavior, and to search for the neural mechanisms for memory encoding, storage and retrieval. Second, we will investigate how aversive emotions (such as stress caused by hunger) would affect C. elegans thermotaxis and chemotaxis. Third, we will probe how neuromodulators mediate the dynamics of the neural circuit.

通过内在情绪调节和学习记忆的指引,动物行为展现出很强的可塑性和灵活性。这种对生存环境的自适应特征对生物的生存繁衍至关重要。为研究这一类行为可塑性的神经环路机制,本项目拟利用秀丽线虫模式系统,结合行为学、遗传学和光神经生理学对特定的和学习记忆相关的神经环路进行系统的解析。在前期工作中,我们发现线虫对温度以及化学物质浓度均表现出可靠的学习记忆能力; 并用其自身分布式的神经网络来驱动灵活多变的趋温和趋化行为。更有研究发现,对控制人的负面情绪起重要作用的五羟色胺能有效调节线虫的学习和记忆功能。在本项目的支持下,我们将 (1) 通过发展全脑钙成像和光遗传学的手段来监测和操纵所有相关神经元的活动,并寻找记忆在神经环路中的表达和读取方式; (2)分析负面情绪(如饥饿所产生的焦虑)是如何改变趋温和趋化行为;(3)相关的神经调节剂是如何作用在神经环路并改变其动力学性质的。

生物在生活环境中会同时接受到多种信息输入，包括温度信息，化学信息，机械信息等。为更好地适应环境，更好的生存，需要对这些信息进行整合。为探索生物是如何对多种信息进行整合，从而调整自身行为策略以及进一步了解神经系统如何参与这一过程，我们针对秀丽隐杆线虫这类模式生物，将其置于线性温度梯度和线性盐浓度梯度的正交场中，研究其同时接受到温度和盐浓度两种信息输入后的趋向行为策略。我们定量刻画了线虫趋向运动的步长，进行方向改变的次数，角度变化规律以及运动轨迹的弯曲程度等指标，并对相应的神经环路进行探索，找到了一类在信息整合过程中起关键作用的神经元。为了对信息整合过程进行更为深入的了解，我们搭建了一套自由行为下秀丽线虫全脑功能成像系统以及一套小型化的温度梯度和盐浓度梯度正交场的装置，可观测信息整合过程中全脑神经元活动变化，为进一步理解信息整合神经环路机制奠定了扎实的实验和技术基础。