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

项目摘要 癫痫与焦虑高度并存(Gaitatzis，2005)，焦虑对患者的生活质量产生负面影响 这些患者(Johnson，2004)。到目前为止，我们对其背后的机制知之甚少。 合并症。最近的研究提供了强有力的证据，证明网络通信在 杏仁基底外侧核(BLA)和内侧前额叶皮质(MPFC)在调节恐惧和刺激的表达中的作用 焦虑(Stujenske等人，2014；Felix-Ortiz等人，2016)(审查见ToVote等人，2015)。最近 Maguire和Reijmers实验室之间的合作证明了小白蛋白(PV)的作用 中间神经元在恐惧网络沟通与行为转换中的中介作用 《表达恐惧》(Davis，2017)。具体地说，我们证明了沉默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，并需要抑制网络 恐惧的交流，这一发现与恐惧行为表达的增加相关。 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换 在生理条件下。很少有研究研究这种神经回路通讯是如何 在病理条件下变得失调或腐败。在这里，我们建议调查是否 焦虑网络交流的失调可能在癫痫患者的焦虑共病中起作用。我们的 初步数据显示慢性癫痫小鼠BLA中PV中间神经元丢失，我们发现 假设有助于焦虑神经元的重新激活，促进网络沟通和 焦虑的行为表现。

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.