Understand the neural mechanism underlying aggressive motivation

 描述(申请人提供)：攻击性是无脊椎动物和脊椎动物物种的一种与生俱来的社会行为。对于大多数人来说，攻击性是保护他们的 资源，并在出现干扰时确保繁殖成功。然而，对于一些人来说，攻击性似乎是一种快乐的来源。许多例子表明，从鱼类到灵长类动物，各种物种中的某些人都会自愿寻找机会从事攻击性行动。对于人类来说，欺凌、跟踪和性掠夺是对我们的社会产生负面影响的多种形式的攻击性行为。抑制攻击性行为的治疗将特别有用，因为它们可以防止潜在的攻击性行为，而不会损害一般的社会、认知和运动能力。不幸的是，关于是什么大脑活动促进了攻击性寻求行为，人们知之甚少，因此，目前还没有专门抑制攻击性动机的治疗方法。为了应对这种知识鸿沟，我们的研究试图了解攻击性冲动是如何出现在大脑中的。在我们以前的研究中，我们发现下丘脑腹内侧腹外侧部(VMHvl)对于男性之间的攻击是不可或缺的。虽然激活VMHvl会导致对男性和女性同种特异性的急性攻击，但抑制VMHvl会减少自然的男性间攻击。然而，目前尚不清楚VMHvl是否只控制攻击的运动表达，还是也决定了非感官的攻击寻求行为。为了解决这个问题，我们设计了一个“自我发起的攻击”(SIA)任务，允许我们暂时将攻击的寻求阶段和行动阶段分开。在任务中，这只动物学会自愿戳鼻子，以接近它们可以攻击的较弱的入侵者。通过这项任务，我们发现VMHvl活动在很大程度上可以调节小鼠的攻击动机。在这项研究中，我们将在这些初步发现的基础上，在单细胞和群体水平上研究SIA任务期间VMHvl细胞的自然活动。通过这项研究 我们希望为攻击性动机的神经起源提供一些新的线索。

 DESCRIPTION (provided by applicant): Aggression is an innate social behavior across invertebrate and vertebrate species. For most individuals, aggression is essential to protect their resources and ensure reproductive success when interference arises. However, for some individuals, aggression appears to be a source of pleasure. Many examples show that certain individuals across a range of species, from fish to primates, will voluntarily seek out the opportunity to engage in aggressive actions. For humans, bullying, stalking, and sexual predation are among the many forms of aggression-seeking behaviors that negatively affect our society. Treatments that suppress aggression-seeking behaviors would be especially useful given that they could prevent potential aggressive actions without compromising general social, cognitive, and motor abilities. Unfortunately, little is known about what brain activity promotes the aggression-seeking behavior and consequently no treatment is currently available to specifically suppress aggressive motivation. In response to this knowledge gap, our studies seek to understand how the aggressive impulses emerge in the brain. In our previous studies, we identified the ventrolateral part of the ventromedial hypothalamus (VMHvl) as being indispensable for inter-male attack. Whereas activation of the VMHvl induces acute attack towards both male and female conspecifics, suppression of the VMHvl reduces natural inter-male attack. However, it remains unclear whether the VMHvl only controls the motor expression of attack or also determines sensory-independent aggression- seeking behaviors. To address this question, we designed a "self-initiated aggression" (SIA) task that allows us to temporarily separate the seeking phase and the action phase of aggression. During the task, the animal learns to voluntarily nose poke to gain access to a weaker intruder that they can attack. Using this task, we found that the VMHvl activity can substantially modulate the aggressive motivation in mice. In this study we will follow up on these initial findings and examine the natural VMHvl cell activity during the SIA task at both the single-cell and population levels. Through this study we hope to shed some new light onto the neural origin of aggressive motivation.