Projections from Infralimbic Cortex to Paraventricular Thalamus Mediate Fear Extinction Retrieval
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ORIGINAL ARTICLE
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
Received: 7 February 2020 / Accepted: 6 March 2020 Ó Shanghai Institutes for Biological Sciences, CAS 2020
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. Electronic supplementary material The online version of this article (https://doi.org/10.1007/s12264-020-00603-6) contains supplementary material, which is available to authorized users. Yan Tao, Cheng-Yun Cai and Jia-Yun Xian contributed equally to this work. & Dong-Ya Zhu [email protected] 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
Keywords Paraventricular thalamus Infralimbic cortex Medial prefrontal cortex Amygdala Fear extinction retrieval Neural circuit Post-traumatic stress disorder
Introduction Fear can be elicited by perceived threats. Proper behavioral responses to threats enable all animals, including humans, to reduce the risk of danger and increase the chance of survival [1]. When individuals are unable to overcome acquired fear, they may develop fear-related disorders [2]. Post-traumatic stress disorder (PTSD) is a highly prevalent fear-related disorder, costing affected individuals a lot [3]. Fear extinction is the first-line treatment for PTSD patients under the term ‘‘exposure therapy’’ [4]. Prolonged Exposure (PE) and Virtual Reality Exposure (VRE) have been highly effective in recent years [5]. Besides, pharmacological interventions, such as paroxetine, venlafaxine and fluoxetine, are also used to treat
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