Projections from Infralimbic Cortex to Paraventricular Thalamus Mediate Fear Extinction Retrieval

• Published in: Neuroscience bulletin Vol. 37; no. 2; pp. 229 - 241
• Main Authors: Tao, Yan, Cai, Cheng-Yun, Xian, Jia-Yun, Kou, Xiao-Lin, Lin, Yu-Hui, Qin, Cheng, Wu, Hai-Yin, Chang, Lei, Luo, Chun-Xia, Zhu, Dong-Ya
• Format: Journal Article
• Language: English
• Published: Singapore Springer Singapore 01.02.2021; Springer
• Subjects: Anatomy; Anesthesiology; Biomedical and Life Sciences; Biomedicine; Central Amygdaloid Nucleus; Extinction, Psychological; Fear; Human Physiology; Neural circuitry; Neurology; Neurons; Neurosciences; Original; Original Article; Pain Medicine; Prefrontal Cortex; Thalamus; Medial prefrontal cortex; Amygdala; Paraventricular thalamus; Infralimbic cortex; Post-traumatic stress disorder; Neural circuit; Fear extinction retrieval
• ISSN: 1673-7067; 1995-8218
• DOI: 10.1007/s12264-020-00603-6

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.