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: 9908194
• 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/9908194
• 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.

项目概要 癫痫与焦虑高度共存（Gaitatzis，2005），这对人们的生活质量产生负面影响 这些患者（Johnson，2004）。迄今为止，我们对其背后的机制知之甚少 合并症。最近的研究为网络通信在人与人之间的作用提供了有力的证据。 基底外侧杏仁核（BLA）和内侧前额叶皮层（mPFC）在介导恐惧和表达方面 焦虑（Stujenske 等人，2014 年；Felix-Ortiz 等人，2016 年）（综述参见（Tovote 等人，2015 年））。最近的一个 Maguire 和 Reijmers 实验室之间的合作证明了小清蛋白 (PV) 的作用 中间神经元介导恐惧的网络交流和行为之间的转变 恐惧的表达（戴维斯，2017）。具体来说，我们证明沉默 BLA 中的 PV 中间神经元 增加恐惧神经元在灭绝后的重新激活，并且需要抑制网络 恐惧的交流，与恐惧的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转变 生理条件下。很少有研究调查这种神经回路通讯如何发挥作用 在病理条件下变得失调或腐败。在此我们建议调查是否 焦虑网络交流的失调可能在癫痫共病焦虑中发挥作用。我们的 初步数据表明，我们在慢性癫痫小鼠的 BLA 中发现了 PV 中间神经元的损失。 假设促进焦虑神经元的重新激活，促进网络交流和 焦虑的行为表现。