Disruption in the network communication of safety in epilepsy with comorbid anxiety

癫痫伴共病焦虑的安全网络交流中断

• 批准号: 10360630
• 负责人: Jamie Lynn Maguire
• 金额: $ 39.29万
• 依托单位: TUFTS UNIVERSITY BOSTON
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-04-15 至 2023-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10360630
• 关键词: Amygdaloid structure; Anti-Anxiety Agents; Anxiety; Attention; Automobile Driving; Behavioral; Cell Density; Chronic; Communication; Communication impairment; Coupling; Data; Development; Epilepsy; Exposure to; Extinction (Psychology); Fright; Functional disorder; Hippocampus (Brain); Incidence; Injections; Interneurons; Knowledge; Measures; Medial; Mediating; Mental Depression; Mental disorders; Molecular Profiling; Mus; Neurons; Parvalbumins; Pathologic; Patients; Physiological; Play; Prefrontal Cortex; Quality of life; Reporting; Role; Safety; Testing; Tetanus Helper Peptide; anxiety-like behavior; communication behavior; comorbid depression; comorbidity; excessive anxiety; experience; neural circuit; optogenetics; pre-clinical research

Project Summary Epilepsy is highly comorbid with anxiety (Gaitatzis, 2005), which negatively impacts the quality of life of these patients (Johnson, 2004). To-date, we have little knowledge of the mechanisms underlying this comorbidity. Recent studies provide strong evidence for a role of network communciation between the basolateral amygdala (BLA) and the medial prefrontal cortex (mPFC) in mediating the expression of fear and anxiety (Stujenske et al., 2014;Felix-Ortiz et al., 2016) (for review see (Tovote et al., 2015)). A recent collaborative effort between the Maguire and Reijmers' labs demonstrates a role for parvalbumin (PV) interneurons in mediating the transition between the network communication of fear and the behavioral expression of fear (Davis, 2017). Specifically, we demonstrate that silencing PV interneurons in the BLA increase the reactivation of fear neurons following extinction and are required to suppress the network communication of fear, findings which are correlated with an increase in the behavioral expression of fear. These studies have largely focused on transitions between states of safety and states of fear and anxiety under physiological conditions. Few studies have investigated how this neural circuit communication may become dysregulation or corrupted under pathological conditions. Here we propose to investigate whether dysregulation in the network communication of anxiety may play a role in comorbid anxiety in epilepsy. Our preliminary data demonstrates a loss of PV interneurons in the BLA of chronically epileptic mice which we hypothesize facilitates the reactivation of anxiety neurons, promoting the network communication and the behavior expression of anxiety.

项目摘要 癫痫与焦虑高度合并（Gaitatzis，2005），这对生活质量产生了负面影响 这些患者（Johnson，2004）。迄今为止，我们对此的机制知之甚少 合并症。最近的研究提供了有力的证据，证明了网络通讯的作用 基底外侧杏仁核（BLA）和内侧前额叶皮层（MPFC）介导恐惧的表达和 焦虑（Stujenske等，2014； Felix-Ortiz等，2016）（有关评论，请参见（Tovote等，2015））。最近 Maguire和Reijmers实验室之间的合作努力展示了Parvalbumin（PV）的角色 中间神经元调解恐惧的网络交流与行为的过渡 恐惧的表达（戴维斯，2017年）。具体而言，我们证明了在BLA中沉默的PV中间神经元 增加灭绝后恐惧神经元的重新激活，需要抑制网络 恐惧的交流，与恐惧行为表达的增加相关的发现。 这些研究主要集中在安全状态与恐惧和焦虑状态之间的过渡 在生理条件下。很少有研究调查了这种神经回路的通信如何 在病理状况下变失调或损坏。在这里，我们建议调查是否 焦虑网络交流中的失调可能在癫痫的合并症焦虑中起作用。我们的 初步数据表明，在慢性癫痫小鼠的BLA中，PV中间神经元丧失了我们 假设化促进焦虑神经元的重新激活，促进网络交流和 焦虑的行为表达。