Research Supplement to Promote Diversity in Health-Related Research

摘要报表 攻击性是脊椎动物物种与生俱来的社会行为。然而，过度 攻击性--从校园欺凌到恐怖袭击--给我们的 社会。患有某些精神障碍的个人，如双相情感障碍和后遗症 创伤应激障碍，更有可能采取暴力行动，危及自己和那些 在他们周围。虽然经典的侵略模式长期以来一直表明不适当的 攻击性源于“自上而下”的攻击性执行控制功能障碍--相关 电路，几乎没有直接的生理或神经电路证据来支持这一点。在这里，我们将 采用另一种“自下而上”的方法来研究 在攻击性中有明确作用的神经轨迹。我们假设这些抑制性控制是 确保在正确的时间和针对正确的目标表达攻击性至关重要。我们 已确定下丘脑腹内侧腹外侧部(VMHvl)是 “反应性”和“主动性”攻击性的轨迹。而光基因激活 VMHvl对攻击行为和攻击寻求行为均有促进作用，对VMHvl的抑制作用更强 结果适得其反。在这项研究中，我们将讨论局部和远程抑制输入是如何 调节VMHvl细胞的反应，从而调节攻击行为。虽然神经元 在VMHv1主要是兴奋性的，VMHv1直接和强烈地被VMHv1抑制 位于VMHvl核外侧和腹侧的“壳”神经元。因此，我们假设 VMHvl外壳处于很好的位置，可以塑造兴奋性VMHvl中与攻击相关的活动 神经元。在研究的第一部分，我们将使用活体记录，功能操作， 视紫红质辅助的通道电路图，和病毒示踪确定之间的关系 这是VMHv1的抑制性外壳和兴奋性“核心”。在研究的第二部分，我们将 缩小并检查VMHvl的远程抑制输入的功能。具体来说，我们 将检验这样一种假设，即来自内侧视前区、下丘脑的抑制性输入 对生殖和父母照料至关重要的区域，对于抑制VMHvl反应是必不可少的 针对不适当的攻击目标，防止误导攻击。总而言之，这项研究 将提供一个急需的框架来理解抑制机制是如何控制 攻击性行为，并为新型电路级攻击疗法铺平道路 控制力。

SUMMARY STATEMENT Aggression is an innate social behavior across vertebrate species. However, excessive aggression—ranging from school bullying to terrorist attacks—imposes a devastating risk to our society. Individuals with certain psychiatric disorders, such as bipolar disorder and post- traumatic stress disorder, are more likely to act violently, jeopardizing their own lives and those around them. While classic models of aggression have long-suggested that improper aggression results from dysfunction of “top-down” executive control of aggression-relevant circuitry, there is little direct physiological or neural circuit evidence to support this. Here, we will take an alternative “bottom-up” approach to investigate the inhibitory control impinged onto a neural locus with a clear role in aggression. We hypothesize that these inhibitory controls are essential to ensure aggression is expressed at the right time and towards the right target. We have identified the ventrolateral part of the ventromedial hypothalamus (VMHvl) as an essential locus for both “reactive” and “proactive” aggression. Whereas optogenetic activation of the VMHvl can promote both attack and aggression-seeking behavior, VMHvl inhibition has the opposite effect. In this study, we will address how local and long-range inhibitory inputs modulate responses of VMHvl cells, and consequently aggressive behaviors. Although neurons in the VMHvl are primarily excitatory, the VMHvl is directly and strongly inhibited by VMHvl “shell” neurons that are situated lateral and ventral to the VMHvl core. Thus, we hypothesize that the VMHvl shell is well positioned to shape aggression-relevant activity in excitatory VMHvl neurons. In the first part of the study, we will employ in vivo recording, functional manipulation, channelrhodopsin-assisted circuit mapping, and viral tracing to define the relationship between this inhibitory shell and excitatory “core” of the VMHvl. In the second part of the study, we will zoom out and examine the function of long-range inhibitory inputs to the VMHvl. Specifically, we will test the hypothesis that the inhibitory inputs from the medial preoptic area, a hypothalamic region critical for reproduction and parental care, is essential for suppressing VMHvl responses towards improper aggression targets and preventing misdirected attack. In summary, this study will provide a much needed framework to understand how inhibitory mechanisms control aggressive behavior, and pave the way for new types of circuit-level therapeutics for aggression control.