Department of Psychological and Brain Sciences, Texas A&M University, College Station, TX, USA.
Institute for Neuroscience, Texas A&M University, College Station, TX, USA.
Nat Commun. 2023 Oct 17;14(1):6565. doi: 10.1038/s41467-023-42315-1.
Traumatic events result in vivid and enduring fear memories. Suppressing the retrieval of these memories is central to behavioral therapies for pathological fear. The medial prefrontal cortex (mPFC) and hippocampus (HPC) have been implicated in retrieval suppression, but how mPFC-HPC activity is coordinated during extinction retrieval is unclear. Here we show that after extinction training, coherent theta oscillations (6-9 Hz) in the HPC and mPFC are correlated with the suppression of conditioned freezing in male and female rats. Inactivation of the nucleus reuniens (RE), a thalamic hub interconnecting the mPFC and HPC, reduces extinction-related Fos expression in both the mPFC and HPC, dampens mPFC-HPC theta coherence, and impairs extinction retrieval. Conversely, theta-paced optogenetic stimulation of RE augments fear suppression and reduces relapse of extinguished fear. Collectively, these results demonstrate a role for RE in coordinating mPFC-HPC interactions to suppress fear memories after extinction.
创伤性事件会导致生动而持久的恐惧记忆。抑制这些记忆的提取是病理性恐惧行为疗法的核心。内侧前额叶皮层（mPFC）和海马体（HPC）被认为与检索抑制有关，但在消退检索过程中 mPFC-HPC 活动如何协调尚不清楚。在这里，我们发现，在消退训练后，雄性和雌性大鼠的 HPC 和 mPFC 中的相干 theta 振荡（6-9 Hz）与条件性冻结的抑制相关。内侧前连合核（RE）的失活，一个连接 mPFC 和 HPC 的丘脑中枢，减少了两者中与消退相关的 Fos 表达，抑制了 mPFC-HPC 的 theta 相干，并损害了消退检索。相反，RE 的 theta 节拍光遗传学刺激增强了恐惧抑制，并减少了已消退的恐惧的复发。总的来说，这些结果表明，RE 在协调 mPFC-HPC 相互作用以抑制消退后恐惧记忆方面发挥作用。
