Adaptive behaviour necessitates the formation of memories for fearful events, but also that these memories can be extinguished. Effective extinction prevents excessive and persistent reactions to perceived threat, as can occur in anxiety and ‘trauma- and stressor-related’ disorders¹. However, although there is evidence that fear learning and extinction are mediated by distinct neural circuits, the nature of the interaction between these circuits remains poorly understood^2,3,4,5,6. Here, through a combination of in vivo calcium imaging, functional manipulations, and slice physiology, we show that distinct inhibitory clusters of intercalated neurons (ITCs) in the mouse amygdala exert diametrically opposed roles during the acquisition and retrieval of fear extinction memory. Furthermore, we find that the ITC clusters antagonize one another through mutual synaptic inhibition and differentially access functionally distinct cortical- and midbrain-projecting amygdala output pathways. Our findings show that the balance of activity between ITC clusters represents a unique regulatory motif that orchestrates a distributed neural circuitry, which in turn regulates the switch between high- and low-fear states. These findings suggest that the ITCs have a broader role in a range of amygdala functions and associated brain states that underpins the capacity to adapt to salient environmental demands.

适应性行为需要形成对可怕事件的记忆，但这些记忆也可以消失。有效的消退可以防止对感知到的威胁的过度和持续的反应，这可能发生在焦虑和“与创伤和压力源相关的”疾病¹中。然而，尽管有证据表明恐惧学习和消退是由不同的神经回路介导的，但这些回路之间相互作用的性质仍然知之甚少^2,3,4,5,6. 在这里，通过体内钙成像、功能操作和切片生理学的结合，我们表明小鼠杏仁核中不同的嵌入神经元 (ITC) 抑制簇在恐惧消退记忆的获取和检索过程中发挥着截然相反的作用。此外，我们发现 ITC 簇通过相互突触抑制相互拮抗，并以不同的方式访问功能上不同的皮质和中脑投射杏仁核输出通路。我们的研究结果表明，ITC 集群之间的活动平衡代表了一种独特的调节基序，该基序协调了分布式神经回路，进而调节了高恐惧状态和低恐惧状态之间的切换。