Deconstruction of a Neural Circuit for Aggression

摘要报表 攻击性是一种先天的社会行为，见于脊椎动物物种。虽然这是一个必不可少的 竞争资源和自卫的手段，侵略也是一种代价高昂的行为 潜在的致命后果。因此，对动物来说，将攻击引向 正确的目标，最大限度地增加利益，最大限度地减少与战斗相关的风险。在人类身上， 误入歧途的攻击尤其具有破坏性，因为它通常针对的是 一个人的生活--配偶、孩子、照顾者，甚至是自己。这种误入歧途的攻击性可能会使人紧张 并造成巨大的身体和精神压力。例如，具有以下特征的个人 某些精神障碍，如双相情感障碍和创伤后应激障碍， 更有可能表现出错误的攻击性，危及自己和他人的生命。目标是 当前项目的主要目的是阐明允许动物 产生适当的定向攻击性。这样做涉及多个行为过程。在……里面 以老鼠为例，社交团体中的个人首先了解每个成员的社会地位 通过重复的激励性相互作用。然后，在随后的相遇中，它们识别 对手的社会地位，并使用这些信息来确定是否发动攻击。这里, 我们将研究支持这些行为过程的每一个神经机制 最终允许老鼠有选择地发起攻击。鉴于众所周知的多巴胺在脑内的作用 强化学习，目标1将解决腹侧被盖区是否存在多巴胺 (VTA)在战斗结果为基础的社会学习和攻击性中起着重要作用 表情。我们将使用系统的方法来确定多巴胺作用的关键部位(S)。 调节攻击性。目标2将研究社会地位信息的神经表征， 特别关注视前内侧核的后部，这是一个关键的上游 攻击回路中多个节点的区域。在目标3中，我们将研究 PMPOA投射通过特定路径的光基因操作引导攻击。在……里面 综上所述，这项研究将揭示社会地位信息是如何在大脑中呈现和使用的 将攻击性引向正确的社会目标。它进一步承诺提供新的 了解多巴胺在攻击性和相关社会学习中的作用。如果成功，我们的 拟议的研究将为攻击性的精细神经控制提供新的见解，以及 可能会产生新的治疗目标，以抑制夸大和错误的攻击 伴随着一些精神疾病。

SUMMARY STATEMENT Aggression is an innate social behavior seen across vertebrate species. Although an essential means to compete for resources and defend oneself, aggression is also a costly behavior with potentially deadly consequences. Hence, it is important for animals to direct aggression toward the correct targets to maximize benefits and minimize risk associated with fighting. In humans, misdirected aggression is particularly destructive as it often targets the most important people in one’s life—spouse, children, caregivers, or even oneself. Such misdirected aggression can strain relationship and cause tremendous physical and mental stress. For example, individuals with certain psychiatric disorders, such as bipolar disorder and post-traumatic stress disorder, are more likely to express misdirected aggression, jeopardizing their own and others' lives. The goal of the current project is to elucidate the neural mechanisms that allow an animal to generate properly directed aggression. Doing so involves multiple behavioral processes. In mice, for example, individuals in a social group first learn the social status of each member through repeated agonistic interactions. Then, in subsequent encounters, they recognize the social status of an opponent and use this information to determine whether to initiate attack. Here, we will investigate the neural mechanisms supporting each of these behavioral processes that ultimately allow mice to selectively initiate aggression. Given the well-known role of dopamine in reinforcement learning, Aim 1 will address whether dopamine from the ventral tegmental area (VTA) plays an important role in fighting-outcome-based social learning and aggression expression. We will use a systematic approach to identify the key site(s) of dopamine action in modulating aggression. Aim 2 will examine the neural representation of social status information, with particular focus on the posterior part of the medial preoptic nucleus (pMPOA), a key upstream region of multiple nodes in the aggression circuit. In Aim 3, we will examine the functional role of pMPOA projections in directing aggression via pathway-specific optogenetic manipulation. In summary, this study will reveal how social status information is represented in the brain and used to direct aggression toward the right social targets. It further promises to provide new understanding of dopamine's role in aggression and associated social learning. If successful, our proposed investigations will provide new insight into the fine neural control of aggression, and may yield new therapeutic targets for suppressing the exaggerated and mistargeted aggression accompanying some psychiatric conditions.