FEAR LEARNING IN MICE AND DISORDERS OF FEAR IN HUMANS

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 在报告期内，我们完成了在猕猴杏仁核中使用慢病毒载体的基因治疗方法的试点试验。 这些数据将很快汇总成一份简短的报告，并可能作为未来NIH R21研究的试点数据。 我们继续我们以前对可塑性因子BDNF的研究，它与NMDA一起沿着在介导恐惧的可塑性和恐惧的消失中的作用也持续了一整年。 我们沿着这条道路的主要发现之一是利用小分子TrkB激动剂7，8 DHF，它可以穿过血脑屏障并激活大脑内的TrkB受体。 我们发现这种药物可以增强突触可塑性和情绪学习和记忆。 目前正在讨论将这些化合物转化为人类的可能性。 另一个最近的发现是，与压力相关的神经肽PACAP与人类的创伤后应激障碍有关，并且在经历恐惧学习的小鼠中其表达发生了变化。

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.