Department of Neuroscience, City University of Hong Kong, Hong Kong 999077, China.
Department of Biomedical Sciences, City University of Hong Kong, Hong Kong 999077, China.
Int J Mol Sci. 2022 May 17;23(10):5578. doi: 10.3390/ijms23105578.
The medial prefrontal cortex (mPFC) and β-adrenoceptors (βARs) have been implicated in modulating anxiety-like behavior. However, the specific contributions of the β2-AR subtype in mPFC in anxiety are still unclear. To address this issue, we used optogenetic and microRNA-based (miRNA) silencing to dissect the role of β2-AR in mPFC in anxiety-like behavior. On the one hand, we use a chimeric rhodopsin/β2-AR (Opto-β2-AR) with in vivo optogenetic techniques to selectively activate β2-adrenergic signaling in excitatory neurons of the mPFC. We found that opto-activation of β2-AR is sufficient to induce anxiety-like behavior and reduce social interaction. On the other hand, we utilize the miRNA silencing technique to specifically knock down the β2-AR in mPFC excitatory neurons. We found that the β2-AR knock down induces anxiolytic-like behavior and promotes social interaction compared to the control group. These data suggest that β2-AR signaling in the mPFC has a critical role in anxiety-like states. These findings suggest that inhibiting of β2-AR signaling in the mPFC may be an effective treatment of anxiety disorders.
内侧前额叶皮层（mPFC）和β-肾上腺素受体（βARs）被认为可以调节焦虑样行为。然而，mPFC 中β2-AR 亚型在焦虑中的具体作用仍不清楚。为了解决这个问题，我们使用光遗传学和基于 microRNA 的（miRNA）沉默技术来剖析 mPFC 中β2-AR 在焦虑样行为中的作用。一方面，我们使用一种嵌合视蛋白/β2-AR（Opto-β2-AR），结合体内光遗传学技术，选择性地激活 mPFC 中兴奋性神经元的β2-肾上腺素能信号。我们发现，β2-AR 的光激活足以诱导焦虑样行为并减少社交互动。另一方面，我们利用 miRNA 沉默技术，特异性地敲低 mPFC 兴奋性神经元中的β2-AR。我们发现，与对照组相比，β2-AR 敲低诱导出抗焦虑样行为并促进社交互动。这些数据表明，mPFC 中的β2-AR 信号在焦虑样状态中起着关键作用。这些发现表明，抑制 mPFC 中的β2-AR 信号可能是治疗焦虑障碍的有效方法。
