Huang Yen-Ling, Liu Yu-Rui, Chang Chun-Hui
Institute of Systems Neuroscience, National Tsing Hua University, Hsinchu 30013, Taiwan.
Institute of Systems Neuroscience, National Tsing Hua University, Hsinchu 30013, Taiwan; Brain Research Center, National Tsing Hua University, Hsinchu 30013, Taiwan.
Neuroscience. 2025 Aug 5;583:93-102. doi: 10.1016/j.neuroscience.2025.07.048.
The perirhinal cortex (PRC) and the thalamic reuniens (Re)/rhomboid (Rh) nuclei (ReRh) participate in the regulation of trace fear learning, likely through their respective reciprocal interconnections with the medial prefrontal cortex (mPFC) and the hippocampus (HPC). We previously demonstrated that ReRh inactivation impaired the acquisition, but not the retrieval, of trace fear memory. Moreover, the retrieval of trace fear memory acquired under ReRh inactivation only reprised when the ReRh was brought off-line. To explore the role of the PRC in trace fear regulation, we pharmacologically inactivated the PRC before trace fear acquisition and/or retrieval in this study. Our results showed that PRC inactivation during either phase resulted in a decrease in fear response during the early test session compared to controls. We also noticed that without the proper function of the PRC during both the acquisition and retrieval, the rats displayed a high level of fear during the early test session but declined rapidly toward the latter trials compared to controls. The results suggested that although the retrieval of trace fear memory acquired under PRC inactivation recurred during PRC inactivation, the fear memory was relatively fragile. Finally, for rats with or without functional PRC, disruption of NMDA-dependent plasticity in the dorsal HPC (DH) during conditioning resulted in defects of trace fear learning in both scenarios. Collectively, our results indicated that functional PRC is involved in the regulation of trace fear acquisition and retrieval, and that trace fear acquisition is hippocampus-dependent regardless of the PRC being on-line or off-line.
嗅周皮质(PRC)和丘脑连合核(Re)/菱形核(Rh)(ReRh)可能通过它们与内侧前额叶皮质(mPFC)和海马体(HPC)各自的相互连接参与痕迹恐惧学习的调节。我们之前证明,ReRh失活会损害痕迹恐惧记忆的获得,但不会损害其提取。此外,只有当ReRh离线时,在ReRh失活条件下获得的痕迹恐惧记忆的提取才会重现。为了探究PRC在痕迹恐惧调节中的作用,在本研究中,我们在痕迹恐惧获得和/或提取之前对PRC进行了药物失活处理。我们的结果表明,与对照组相比,在任何一个阶段PRC失活都会导致早期测试阶段恐惧反应的降低。我们还注意到,在获得和提取过程中如果没有PRC的正常功能,大鼠在早期测试阶段会表现出高度恐惧,但与对照组相比,在后续试验中恐惧迅速下降。结果表明,虽然在PRC失活期间在PRC失活条件下获得的痕迹恐惧记忆的提取会重现,但恐惧记忆相对脆弱。最后,对于有或没有功能性PRC的大鼠,在条件反射过程中背侧海马体(DH)中NMDA依赖性可塑性的破坏在两种情况下都会导致痕迹恐惧学习的缺陷。总的来说,我们的结果表明功能性PRC参与了痕迹恐惧获得和提取的调节,并且无论PRC是在线还是离线,痕迹恐惧获得都依赖于海马体。