上丘PV+神经元引发“战斗-逃跑”反应的神经环路机制

“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。

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.