β2-Adrenoceptors in the Medial Prefrontal Cortex Excitatory Neurons Regulate Anxiety-like Behavior in Mice

The medial prefrontal cortex (mPFC) and beta-adrenoceptors (beta ARs) have been implicated in modulating anxiety-like behavior. However, the specific contributions of the beta 2-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 beta 2-AR in mPFC in anxiety-like behavior. On the one hand, we use a chimeric rhodopsin/beta 2-AR (Opto-beta 2-AR) with in vivo optogenetic techniques to selectively activate beta 2-adrenergic signaling in excitatory neurons of the mPFC. We found that opto-activation of beta 2-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 beta 2-AR in mPFC excitatory neurons. We found that the beta 2-AR knock down induces anxiolytic-like behavior and promotes social interaction compared to the control group. These data suggest that beta 2-AR signaling in the mPFC has a critical role in anxiety-like states. These findings suggest that inhibiting of beta 2-AR signaling in the mPFC may be an effective treatment of anxiety disorders.