Wang Zongliang, Wang Zeyi, Zhou Qiang
State Key Laboratory of Chemical Oncogenomics, Guangdong Provincial Key Laboratory of Chemical Genomics, Peking University Shenzhen Graduate School, Shenzhen, 518055, China.
Neuropsychopharmacology. 2024 May;49(6):961-973. doi: 10.1038/s41386-023-01790-2. Epub 2024 Jan 5.
Distinguishing between cues predicting safety and danger is crucial for survival. Impaired learning of safety cues is a central characteristic of anxiety-related disorders. Despite recent advances in dissecting the neural circuitry underlying the formation and extinction of conditioned fear, the neuronal basis mediating safety learning remains elusive. Here, we showed that safety learning reduces the responses of paraventricular thalamus (PVT) neurons to safety cues, while activation of these neurons controls both the formation and expression of safety memory. Additionally, the PVT preferentially activates prefrontal cortex somatostatin interneurons (SOM-INs), which subsequently inhibit parvalbumin interneurons (PV-INs) to modulate safety memory. Importantly, we demonstrate that acute stress impairs the expression of safety learning, and this impairment can be mitigated when the PVT is inhibited, indicating PVT mediates the stress effect. Altogether, our findings provide insights into the mechanism by which acute stress modulates safety learning.
区分预测安全和危险的线索对生存至关重要。安全线索学习受损是焦虑相关障碍的核心特征。尽管在剖析条件性恐惧形成和消退背后的神经回路方面取得了最新进展，但介导安全学习的神经元基础仍然难以捉摸。在这里，我们表明安全学习会降低室旁丘脑（PVT）神经元对安全线索的反应，而这些神经元的激活控制着安全记忆的形成和表达。此外，PVT优先激活前额叶皮质生长抑素中间神经元（SOM-INs），随后这些中间神经元抑制小白蛋白中间神经元（PV-INs）来调节安全记忆。重要的是，我们证明急性应激会损害安全学习的表达，而当PVT受到抑制时这种损害可以减轻，这表明PVT介导了应激效应。总之，我们的研究结果为急性应激调节安全学习的机制提供了见解。
