Neural Circuits Controlling Resiliency in Dominant Animals

 描述（由申请人提供）：暴露于压力事件是几种情绪和焦虑症病因的关键因素。然而，并不是所有暴露于压力事件的人都会患上与压力有关的精神疾病，人们对是什么使一些人脆弱而另一些人富有弹性非常感兴趣。在这项提案中，我们将调查的神经基板和细胞机制控制社会压力的抵抗力使用的社会失败模型在叙利亚仓鼠，称为条件性失败。我们以前的研究表明，在边缘下（IL）和边缘前（PL）皮层的神经活动是必要的减少条件性失败反应所表现出的占主导地位的仓鼠。在一般情况下，我们预计，优势关系的维护在特定的神经回路中产生可塑性，从而促进对占主导地位的仓鼠的条件性失败的抵抗。在这个建议中，我们假设，激活IL神经元的传出投射到基底外侧杏仁核（BLA）（即IL-BLA神经回路）和PL神经元的传出投射到中缝背核（DRN）（即PL-DRN神经回路）调节抗性的条件失败占主导地位的仓鼠。我们将测试本提案中的两个具体目标。首先，我们将确定优势仓鼠中升高的失败诱导的神经激活是否发生在IL-至-BLA和/或PL-至-DRN神经回路内。第二，我们将确定是否IL-BLA和/或PL-DRN神经回路的选择性抑制，以防止在占主导地位的仓鼠条件性失败的阻力。这一系列研究将提高我们对控制社会压力抵抗力的神经机制的理解，并将确定预防和治疗与压力相关的精神疾病的新目标。

 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.