Neuronal circuits modulating stress response in zebrafish

对温和的短期压力的反应对动物和人类都是有益的，因为不利的身体和心理事件，即所谓的应激源，会激活对生存至关重要的适应性反应，如避免潜在的威胁。然而，创伤或慢性压力会导致许多疾病，包括精神疾病，如创伤后应激障碍、抑郁症和职业倦怠。总的来说，与压力相关的疾病给个人和社会带来了巨大的负担。由于哺乳动物大脑的大小和复杂性，一直很难全面研究应激对它们的影响。我建议利用斑马鱼幼体大脑的紧凑大小和透明度来了解体内调节应激反应的神经机制。斑马鱼中调节应激反应的神经元回路与哺乳动物在解剖学和功能上具有广泛的同源性。值得注意的是，斑马鱼已经被用来研究压力导致的精神疾病。这个项目的目标是了解下丘脑中的少量带有基因标记的神经元是如何控制对压力的行为反应的，以及它们的功能障碍如何导致病理行为。下丘脑是大脑中集中参与处理应激刺激的区域。

Responses to mild short-term stress are beneficial to animals and humans, since adverse physical and psychological events, known as stressors, activate adaptive reactions essential for survival, such as avoidance of potential threats. However, traumatic or chronic stress can give rise to many disorders, including psychiatric conditions such as post-traumatic stress disorder, depression, and occupational burnout. Collectively, stress-related pathologies represent a great burden for individuals and society. It has been difficult to comprehensively study the effects of stress on mammalian brains, due to their large size and complexity. I propose to take advantage of the compact size and transparency of the larval zebrafish brain to understand the neuronal mechanisms mediating responses to stress in vivo. The neuronal circuits regulating responses to stress in zebrafish share extensive anatomical and functional homologies with mammalian ones. Significantly, zebrafish has been used to study stress-induced mental illness. The goal of this project is to understand how small populations of genetically-labelled neurons in the hypothalamus, a brain region centrally involved in processing stressful stimuli, control behavioral responses to stress, and how their dysfunction leads to pathological behavior.