BDNF-ergic circuits in extinction of active avoidance

BDNF 能回路消除主动回避

• 批准号: 8841097
• 负责人: Luis E. Rosas-Vidal
• 金额: $ 4.05万
• 依托单位: UNIVERSITY OF PUERTO RICO MED SCIENCES
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-15 至 2016-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8841097
• 关键词: Active Learning; Alteplase; Amygdaloid structure; Area; Brain region; Brain-Derived Neurotrophic Factor; DSM-V; Emotional; Extinction (Psychology); Failure; Fright; Goals; Hippocampus (Brain); Knowledge; Measures; Memory; Mental disorders; Modeling; Patients; Peptide Hydrolases; Pharmaceutical Preparations; Post-Traumatic Stress Disorders; Prefrontal Cortex; Production; Proteins; Rattus; Refractory; Regulation; Research; Rodent; Role; Severities; Signal Transduction; Small Interfering RNA; Source; Stimulus; Structure; Symptoms; Synapses; Training; Trauma; Ventral Striatum; Work; avoidance behavior; base; conditioned fear; experience; improved; learning extinction; novel; novel therapeutic intervention; public health relevance; repaired; research study; response

DESCRIPTION (provided by applicant): Deficient BDNF signaling has been associated with extinction failure and with a poor response to extinction- based therapies for PTSD. Deficient hippocampal-prefrontal connectivity has been correlated with PTSD severity. Our recent work in rats suggests that BDNF signaling from the ventral hippocampus (vHPC) to the infralimbic prefrontal cortex (IL) modulates fear extinction. Much of what we understand about the emotional regulation related to PTSD comes from experimental fear conditioning and extinction, which model the hyperarousal and re-experiencing of symptoms of PTSD. Much less is known, however, about excessive avoidance seen in PTSD. In Aim 1, we will investigate the role of BDNF signaling in extinction of avoidance. In Aim 2, we will improve BDNF signaling to facilitate extinction in rats unable to extinguish avoidance responses.

描述（由申请人提供）：不足的BDNF信号传导与灭绝失败有关，并且对基于灭绝的PTSD疗法的反应较差。不足的海马前额外连通性与PTSD的严重程度有关。我们最近在大鼠中的工作表明，BDNF信号从腹侧海马（VHPC）到额叶前额叶皮层（IL）调节恐惧灭绝。我们对与PTSD相关的情绪调节的理解大部分来自实验性的恐惧调节和灭绝，这对PTSD症状的高度和重新体验进行了建模。然而，关于PTSD中过度回避的众所周知。在AIM 1中，我们将研究BDNF信号传导在避免灭绝中的作用。在AIM 2中，我们将改善BDNF信号传导，以促进无法扑灭回避反应的大鼠的灭绝。