FEAR LEARNING IN MICE AND DISORDERS OF FEAR IN HUMANS

点击翻译按钮获取中文摘要

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.