前额叶皮层(PFC)电路提供对威胁反应性的自上而下的控制。这包括ventromedialPFC(vmPFC)电路，在抑制与恐惧相关的行为状态中发挥作用。强啡肽（Dyn）已涉及介导由严重威胁引起的负面影响和适应不良行为，并在边缘回路中表达，包括vmPFC。然而,在我们对vmPFCDyn表达神经元和Dyn传输如何检测威胁和调节防御行为表达的理解中，存在一个关键的知识差距。这里,我们证明了Dyn细胞被威胁广泛激活，并在vmPFC中局部释放Dyn以限制被动防御行为。我们进一步证明了vmPFCDyn介导的信号传导促进了vmPFC网络向恐惧相关状态的转换。总之,我们揭示了以前未知的vmPFCDyn神经元和Dyn神经肽能传递在通过vmPFC网络的状态驱动变化抑制威胁时的防御行为中的作用。
Prefrontal cortical (PFC) circuits provide top-down control of threat reactivity. This includes ventromedial PFC (vmPFC) circuitry, which plays a role in suppressing fear-related behavioral states. Dynorphin (Dyn) has been implicated in mediating negative affect and maladaptive behaviors induced by severe threats and is expressed in limbic circuits, including the vmPFC. However, there is a critical knowledge gap in our understanding of how vmPFC Dyn-expressing neurons and Dyn transmission detect threats and regulate expression of defensive behaviors. Here, we demonstrate that Dyn cells are broadly activated by threats and release Dyn locally in the vmPFC to limit passive defensive behaviors. We further demonstrate that vmPFC Dyn-mediated signaling promotes a switch of vmPFC networks to a fear-related state. In conclusion, we reveal a previously unknown role of vmPFC Dyn neurons and Dyn neuropeptidergic transmission in suppressing defensive behaviors in response to threats via state-driven changes in vmPFC networks.
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