SAFETY SIGNAL LEARNING IN MONKEYS: CORTICAL REGULATION AND ITS DEVELOPMENT

该子项目是利用 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得主要资金， 因此可以在其他CRISP条目中表示。列出的机构是 研究中心，而研究中心不一定是研究者所在的机构。 这个项目的首要目标是修改我们现有的恐惧抑制范式，使其能够纵向使用，首先调查（手术前和手术后）哪些特定的眶额部参与条件抑制的获得和表达（安全信号学习）（R21期）和第二次遵循纵向时，眶额调节的条件性抑制出现在灵长类动物的两性。 我们已经订购了两个新的条件箱，以允许对本项目的动物进行测试，并对这些箱进行了修改，以允许使用通过计算机屏幕提供的多个视觉提示进行测试。 我们还对条件刺激和非条件刺激的传递进行了编程，并且已经获得了9只雌性和2只雄性成年恒河猴来开始实验。过度的恐惧和焦虑，沿着无法克服这些情绪，是许多精神疾病的定义特征，如恐惧症，恐慌症和创伤后应激障碍。 因此，这种范式将使我们和该领域能够研究介导和调节啮齿动物安全信号学习的解剖学、神经递质和分子事件，这些事件可用于开发特定的假设， 在恒河猴身上进行了测试。 恐惧条件反射和恐惧抑制的动物模型为这些现象的研究提供了有用的工具。我们相信这将建立一种新的重要的转化方法，最终开发出治疗创伤后应激障碍（PTSD）等疾病的新疗法，其中无法对安全信号做出反应是其核心症状之一。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The overarching goal of this project is to modify our existing fear inhibition paradigm to permit its use longitudinally, first to investigate (pre- and post-surgery) which specific orbital frontal sectors are involved in the acquisition and expression of conditioned inhibition (safety signal learning) in male and female adult monkeys (R21 phase) and second follow longitudinally when orbital frontal regulation of conditioned inhibition emerged in primates of both sexes. We have ordered two new conditioning boxes to allow the testing of the animals of the present project and have modified these boxes to allow testing using multiple visual cues delivered via a computer screen. We have also programmed the delivery of the conditioned and unconditioned stimuli and have already acquired 9 female and 2 male adult rhesus monkeys to begin the experiments. Excessive fear and anxiety, along with an inability to overcome these emotions, are defining characteristics of many psychiatric disorders such as phobias, panic disorder, and post-traumatic stress disorder. This paradigm will thus allow us, and the field, to look at the anatomy, neurotransmitters, and molecular events that mediate and modulate safety signal learning in rodents that can be used to develop specific hypotheses that can then be tested in rhesus monkeys. Animal models of fear conditioning and fear inhibition provide useful tools for the study of these phenomena. We believe this will establish a new and important translational approach to eventually develop novel treatments for disorders such as post traumatic stress disorder (PTSD), where an inability to respond to safety signals is one of its core symptoms.