Background

Adaptive behavior depends on the delicate and dynamic balance between acquisition and extinction memories. Disruption of this balance, particularly when the extinction of memory loses control over behavior, is the root of treatment failure of maladaptive behaviors such as substance abuse or anxiety disorders. Understanding this balance requires a better understanding of the underlying neurobiology and its contribution to behavioral regulation.

Methods

We microinjected Daun02 in Fos-lacZ transgenic rats following a single extinction training episode to delete extinction-recruited neuronal ensembles in the basolateral amygdala (BLA) and central nucleus of the amygdala (CN) and examined their contribution to behavior in an appetitive Pavlovian task. In addition, we used immunohistochemistry and neuronal staining methods to identify the molecular markers of activated neurons in the BLA and CN during extinction learning or retrieval.

Results

CN neurons were preferentially engaged following extinction, and deletion of these extinction-activated ensembles in the CN but not the BLA impaired the retrieval of extinction despite additional extinction training and promoted greater levels of behavioral restoration in spontaneous recovery and reinstatement. Disrupting extinction processing in the CN in turn increased activity in the BLA. Our results also show a specific role for CN PKCδ+ neurons in behavioral inhibition but not during initial extinction learning.

Conclusions

We showed that the initial extinction-recruited CN ensemble is critical to the acquisition-extinction balance and that greater behavioral restoration does not mean weaker extinction contribution. These findings provide a novel avenue for thinking about the neural mechanisms of extinction and for developing treatments for cue-triggered appetitive behaviors.

中文翻译：

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第一次灭绝事件期间杏仁核中央核神经元群的募集对灭绝表达有持续影响

背景

适应性行为取决于获得记忆和消退记忆之间微妙而动态的平衡。这种平衡的破坏，特别是当记忆的消失失去对行为的控制时，是药物滥用或焦虑症等适应不良行为治疗失败的根源。了解这种平衡需要更好地了解潜在的神经生物学及其对行为调节的贡献。

方法

我们在Fos-lacZ转基因大鼠中显微注射 Daun02，以删除基底外侧杏仁核 (BLA) 和杏仁核 (CN) 中消退募集的神经元群，并检查它们在食欲巴甫洛夫任务中对行为的贡献。此外，我们使用免疫组织化学和神经元染色方法来识别在消退学习或检索过程中 BLA 和 CN 中激活神经元的分子标记。

结果

CN 神经元在灭绝后优先参与，删除 CN 而不是 BLA 中的这些灭绝激活的集合会损害灭绝的恢复，尽管进行了额外的灭绝训练，并促进了自发恢复和恢复中更高水平的行为恢复。破坏 CN 中的消光过程反过来增加了 BLA 中的活性。我们的结果还显示了 CN PKCδ+ 神经元在行为抑制中的特定作用，但在初始消退学习期间没有。

结论

我们表明，最初的灭绝招募 CN 合奏对于获得-灭绝平衡至关重要，并且更大的行为恢复并不意味着更弱的灭绝贡献。这些发现为思考灭绝的神经机制和开发线索触发的食欲行为的治疗方法提供了一条新途径。