FEAR LEARNING IN MICE AND DISORDERS OF FEAR IN HUMANS

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 在报告期间，我们完成了在猕猴杏仁核中使用慢病毒载体进行基因治疗方法的试点试验。这些数据将很快作为一份简短的报告放在一起，并可能作为未来NIH R21研究的试点数据。 我们继续了之前关于可塑性因素BDNF的工作，以及它与NMDA在调节恐惧的可塑性和消除恐惧方面的作用，也持续了一整年。我们在这条道路上的主要发现之一是利用了一种小分子TrkB激动剂7，8DHF，它可以穿过血脑屏障，激活大脑中的TrkB受体。我们证明了这种药物可以增强突触的可塑性以及情绪学习和记忆。有关这些化合物可能被翻译成人类的讨论正在进行中。 另一个最新的发现是，与压力相关的神经肽PACAP与人类创伤后应激障碍有关，在经历恐惧学习的小鼠中，它的表达发生了变化。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. During the reporting period, we completed our pilot trials for gene therapy approaches using lentiviral vectors in the Macaque amygdala. These data will soon be put together as a brief report and will likely serve as pilot data for a future NIH R21 study. We continued our previous work on the plasticity factor, BDNF, and its role along with NMDA in mediating plasticity of fear and extinction of fear, continued throughout the year as well. One of our primary findings along this path, was the utilization of a small molecule TrKB agonist, 7,8DHF, which crosses the blood-brain barrier and activates the TrkB receptors within the brain. We showed that this drug acts to enhance synaptic plasticity and emotional learning and memory. Discussions are ongoing related to potential translation of these compounds to humans. Another very recent discovery is that the stress-related neuropeptide, PACAP, is associated with Posttraumatic Stress Disorder in humans and that it is altered in its expression in mice undergoing fear learning.