Ventromedial hypothalamic neurons control a defensive emotion state.
Ventromedial hypothalamic neurons control a defensive emotion state.
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DOI：
10.7554/elife.06633
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发表时间：
2015-03-06
期刊：
影响因子：
7.7
通讯作者：
Anderson DJ
中科院分区：
文献类型：
--
作者：
Kunwar PS;Zelikowsky M;Remedios R;Cai H;Yilmaz M;Meister M;Anderson DJ
防御行为反映了潜在的情绪状态，比如恐惧。下丘脑在这些行为中发挥着作用，但主流的教科书观点将其描述为上游情绪中心（如杏仁核）的效应器，而不是情绪中心本身。我们使用光遗传学操作来探测一种特定的下丘脑细胞类型的功能，这种细胞类型介导先天防御反应。这些神经元足以驱动多种防御行为，并且需要在不同的环境中进行防御行为。此外，激活这些神经元的行为后果表现出一般情绪状态的特征，包括可扩展性、（负）效价、泛化和持久性。重要的是，这些神经元还可以调节习得的防御行为，进一步驳斥了长期以来认为下丘脑无法支持情绪学习，因此不是情绪中心的说法。这些数据表明，下丘脑在情绪状态的实例化中起着不可或缺的作用，而不仅仅是上游情绪中心的被动效应器。DOI: http://dx.doi.org/10.7554/eLife.06633.001动物已经进化出大量的“防御行为”来应对捕食者的威胁。例如爬行动物伪装自己以避免被发现，鱼类和鸟类成群结队以迷惑捕食者，昆虫释放有毒化学物质，以及人类准备战斗或逃跑。在哺乳动物中，防御行为被认为是由大脑中一个叫做杏仁核的区域调节的。这个结构被称为大脑的“情绪中心”，负责接收和处理来自即将到来的威胁的感官信息。然后，它将如何处理这些威胁的指令发送到大脑的其他区域，包括下丘脑，下丘脑将这些指令传递到控制哺乳动物行为、内分泌和非自愿反应的大脑区域。多年来，人们一直认为下丘脑的作用只是作为杏仁核编码的情绪状态的中继，而不是作为情绪中心本身。然而，Kunwar等人现在借助一种称为光遗传学的技术挑战了这一假设，在这种技术中，光被用来激活特定的遗传标记神经元群体。当用光直接激活醒着的小鼠下丘脑腹内侧的神经元时，这些动物立即冻结和/或逃跑，就像它们面对捕食者一样。鉴于视觉刺激完全绕过了杏仁核，这表明下丘脑必须能够在没有杏仁核输入的情况下产生这种防御反应。冻结和逃跑的反应在许多关键方面与对捕食者的反应相似。老鼠选择避开笼子里它们受到刺激的区域，这表明，就像捕食者一样，这些区域引发了一种不愉快的情绪状态，可能类似于焦虑或恐惧。在刺激停止后，冻结和逃跑还会持续几秒钟，就像对捕食者的冻结和逃跑反应不会在威胁消失后立即停止一样。最后，破坏刺激的目标神经元使小鼠不太可能避开它们的主要捕食者之一——大鼠。这也使动物不那么焦虑。总的来说，研究结果表明，下丘脑可能不仅仅是杏仁核的一个中继，而且“以杏仁核为中心”的情绪处理观点可能需要重新审视。DOI: http://dx.doi.org/10.7554/eLife.06633.002
Defensive behaviors reflect underlying emotion states, such as fear. The hypothalamus plays a role in such behaviors, but prevailing textbook views depict it as an effector of upstream emotion centers, such as the amygdala, rather than as an emotion center itself. We used optogenetic manipulations to probe the function of a specific hypothalamic cell type that mediates innate defensive responses. These neurons are sufficient to drive multiple defensive actions, and required for defensive behaviors in diverse contexts. The behavioral consequences of activating these neurons, moreover, exhibit properties characteristic of emotion states in general, including scalability, (negative) valence, generalization and persistence. Importantly, these neurons can also condition learned defensive behavior, further refuting long-standing claims that the hypothalamus is unable to support emotional learning and therefore is not an emotion center. These data indicate that the hypothalamus plays an integral role to instantiate emotion states, and is not simply a passive effector of upstream emotion centers. DOI: http://dx.doi.org/10.7554/eLife.06633.001 Animals have evolved a large number of ‘defensive behaviors’ to deal with the threat of predators. Examples include reptiles camouflaging themselves to avoid discovery, fish and birds swarming to confuse predators, insects releasing toxic chemicals, and humans readying themselves to fight or flee. In mammals, defensive behaviors are thought to be mediated by a region of the brain called the amygdala. This structure, which is known as the brain's ‘emotion center’, receives and processes information from the senses about impending threats. It then sends instructions on how to deal with these threats to other regions of the brain including the hypothalamus, which pass them on to the brain regions that control the behavioral, endocrine and involuntary responses of the mammal. For many years it has been thought that the role of the hypothalamus is to serve simply as a relay for emotion states encoded in the amygdala, rather than as an emotion center itself. However, Kunwar et al. have now challenged this assumption with the aid of a technique called optogenetics, in which light is used to activate specific populations of genetically labeled neurons. When light was used to directly activate neurons within the ventromedial hypothalamus in awake mice, the animals instantly froze and/or fled, just as they would when faced with a predator. Given that the optical stimulation had completely bypassed the amygdala, this suggested that the hypothalamus must be capable of generating this defensive response without any input from the amygdala. The freezing and fleeing responses resembled the responses to a predator in a number of key ways. Mice chose to avoid areas of their cage in which they had received the stimulation, suggesting that—like a predator—these areas induced an unpleasant emotional state, perhaps akin to anxiety or fear. Freezing and fleeing persisted for several seconds after the stimulation had stopped, just as freezing and fleeing responses to predators do not immediately cease after the threat has gone. And finally, destroying the neurons targeted by the stimulation made mice less likely to avoid one of their main predators, the rat. It also made the animals less anxious. Overall the results suggest that the hypothalamus may be more than simply a relay for the amygdala, and that ‘amygdala-centric’ views of emotion processing may need to be re-visited. DOI: http://dx.doi.org/10.7554/eLife.06633.002