上丘PV+神经元引发“战斗-逃跑”反应的神经环路机制

Fight-or-flight response to environmental threats plays a fundamental role in survival. Little is known about the neural circuits specifically processing threat-relevant sensory information in the mammalian brain. We recently identified parvalbumin-positive (PV+) excitatory projection neurons in mouse superior colliculus (SC) as a key neuronal subtype for detecting looming objects and triggering fear responses. In this proposal, we will extend our study on these SC PV+ neurons. First, with fiber photometry-aided calcium imaging, we will examine how SC PV+ neurons detect natural biological visual threats such as looming object in an impending collision course. Second, with chronic and acute inactivation, we will test if visual signals from SC PV+ neurons are essential for fear responses triggered by natural biological threats. Third, we will morphologically and functionally characterize the projections from SC PV+ neurons to thalamic nuclei, especially the pathway to lateral posterior thalamic nucleus (LPTN), because other investigators recently reported that SC-LPTN pathway may also trigger fear responses. We will also compare the functions of PV+ SC-LPTN and SC-PBGN pathways. Fourth, we will examine the function of pathway PV+ SC-PnO pathway, focusing on their role in arousal elevation, a physiological phenomenon associated with fight-or-flight responses.

“战斗-逃跑”反应是指人和动物在面临生存威胁时表现出的一系列应激行为和应激生理反应，帮助个体更有力地战斗或逃跑，以增加生存概率。过度或反复的“战斗-逃跑”反应能诱发一类称为创伤后压力应激障碍（post-traumatic stress disorder, PTSD）的精神疾病。要揭示PTSD的发病机理，需要首先对引发“战斗-逃跑”反应的脑内神经环路有深入的认识。申请人最近在小鼠视觉中枢上丘中发现一类表达小清蛋白（parvalbumin, PV）的视觉神经元。它们监测视野中的威胁性视觉刺激，激活后引发小鼠的“战斗-逃跑”反应。本项目将采用多种技术手段深入研究上丘PV+神经元如何介导威胁性视觉刺激引发的“战斗-逃跑”反应，并阐明它们引发“战斗-逃跑”反应的神经环路机制。本项目有望为揭示PTSD的发病机理提供重要的理论基础。

“趋利-避害”是一类重要的生命现象, 对个体的生存至关重要，在物种进化中高度保持。哺乳动物大脑如何启动和调控这些本能行为，是神经科学领域里一个重要的科学问题。近四年里，我们以小鼠为模式动物，系统地研究了哺乳动物上丘神经环路在“趋利-避害”本能行为中的功能。我们发现上丘中不同的神经元群体形成一套“阴-阳”环路模块，通过控制下游多个脑区，分别启动“捕食猎物”和“逃避天敌”的本能行为。这些结果初步揭示了大脑启动“趋利-避害”本能行为的神经环路机制，并暗示上丘可能是哺乳类脑中启动“趋利-避害”本能行为的关键中枢之一。这些研究成果已发表在《Nature Communications》（Shang et al., 2018）和《Nature Neuroscience》（Shang et al., 2019）上。项目组成员尚从平为第一作者，项目负责人曹鹏研究员为独立通讯作者。