Projections from Infralimbic Cortex to Paraventricular Thalamus Mediate Fear Extinction Retrieval
Yan Tao1 • Cheng-Yun Cai1 • Jia-Yun Xian1 • Xiao-Lin Kou1 • Yu-Hui Lin1 • Cheng Qin1 • Hai-Yin Wu1 • Lei Chang1 • Chun-Xia Luo1 • Dong-Ya Zhu1,2,3
1 Department of Pharmacology, School of Pharmacy, Nanjing Medical University, Nanjing 211166, China
2 Institution of Stem Cells and Neuroregeneration, Nanjing Medical University, Nanjing 211166, China
3 Guangdong-Hong Kong, Greater Bay Area Center for Brain Science and Brain-Inspired Intelligence-Macao, Guangzhou 510000, China
Abstract
The paraventricular nucleus of the thalamus (PVT), which serves as a hub, receives dense projections from the medial prefrontal cortex (mPFC) and projects to the lateral division of central amygdala (CeL). The infralimbic (IL) cortex plays a crucial role in encoding and recalling fear extinction memory. Here, we found that neurons in the PVT and IL were strongly activated during fear extinction retrieval. Silencing PVT neurons inhibited extinction retrieval at recent time point (24 h after extinction), while activating them promoted extinction retrieval at remote time point (7 d after extinction), suggesting a critical role of the PVT in extinction retrieval. In the mPFC-PVT circuit, projections from IL rather than prelimbic cortex to the PVT were dominant, and disrupting the IL-PVT projection suppressed extinction retrieval. Moreover, the axons of PVT neurons preferentially projected to the CeL. Silencing the PVT-CeL circuit also suppressed extinction retrieval. Together, our findings reveal a new neural circuit for fear extinction retrieval outside the classical IL-amygdala circuit.
Keywords
Paraventricular thalamus; Infralimbic cortex; Medial prefrontal cortex; Amygdala; Fear extinction retrieval; Neural circuit; Post-traumatic stress disorder
