Neural Circuits Controlling Resiliency in Dominant Animals

 描述(由申请人提供)：暴露在应激事件中是几种情绪和焦虑症的病因中的一个关键因素。然而，并不是所有暴露在应激事件中的人都会患上与压力相关的精神疾病，人们对是什么让一些人变得脆弱，另一些人变得有弹性有了相当大的兴趣。在这项提议中，我们将使用叙利亚仓鼠的社会失败模型(称为条件性失败)来研究控制对社会压力的抵抗的神经底物和细胞机制。我们先前的研究表明，下缘(IL)和前额叶(PL)皮质的神经活动是优势仓鼠减少条件性失败反应所必需的。总体而言，我们预计优势关系的维持在特定神经回路中产生可塑性，从而提高优势仓鼠对条件性失败的抵抗力。在这一设想中，我们假设支配优势的仓鼠对杏仁基底外侧核(BLA)有传出投射的IL神经元(即IL-BLA神经回路)和向中缝背核(DRN)有传出投射的PL神经元(即PL-到DRN神经回路)的激活调节对条件性失败的抵抗。我们将测试这项提案中的两个具体目标。首先，我们将确定优势仓鼠中失败诱导的神经激活是否发生在IL-to-BLA和/或PL-to-DRN神经回路中。其次，我们将确定选择性抑制IL-to-BLA和/或PL-to-DRN神经回路是否能阻止优势仓鼠对条件性失败的抵抗。这一系列研究将提高我们对控制社会压力抵抗的神经机制的理解，并将确定预防和治疗与压力相关的精神疾病的新靶点。

 DESCRIPTION (provided by applicant): Exposure to stressful events is a key factor in the etiology of several mood and anxiety disorders. However, not all individuals exposed to stressful events develop stress-related mental illness, and there is considerable interest in what makes some individuals vulnerable and others resilient. In this proposal, we will investigate the neural substrates and cellular mechanisms controlling resistance to social stress using a social defeat model in Syrian hamsters, called conditioned defeat. Our previous research indicates that neural activity in the infralimbic (IL) and prelimbic (PL) cortex is necessary for the reduced conditioned defeat response exhibited by dominant hamsters. In general, we expect that the maintenance of dominance relationships generates plasticity in specific neural circuits that promotes resistance to conditioned defeat in dominant hamsters. In this proposal, we hypothesize that activation of IL neurons with efferent projections to the basolateral amygdala (BLA) (i.e. IL-to-BLA neural circuit) and PL neurons with efferent projections to the dorsal raphe nucleus (DRN) (i.e. PL-to-DRN neural circuit) regulates resistance to conditioned defeat in dominant hamsters. We will test two specific aims in this proposal. First, we will determine whether elevated defeat- induced neural activation in dominant hamsters occurs within IL-to-BLA and/or PL-to-DRN neural circuits. Second, we will determine whether selective inhibition of IL-to-BLA and/or PL-to-DRN neural circuits prevents resistance to conditioned defeat in dominant hamsters. This line of research will improve our understanding of the neural mechanisms controlling resistance to social stress and will identify novel targets for the prevention and treatment of stress-related mental illness.