A ventral hippocampus-basolateral amygdala circuit regulates the unconditioned stimulus retrieval-induced reconsolidation of remote fear memory

作者：Dan Guo, Zhong Wang, Fanglin Liu, Wen‐Hao Chen, Xuejiao Gao, Shihao Huang, Serik Tabarak, Yuan Yao, Shiya Zhang, Jie Shi, Lin Lü, Ying Han · 发表于：Journal of Advanced Research · 年份：2025 · DOI：10.1016/j.jare.2025.10.015 · 被引用次数：2 · 研究领域：Memory and Neural Mechanisms、Neuroscience and Neuropharmacology Research、Stress Responses and Cortisol

• Propranolol after US retrieval potently and lastingly disrupted remote fear memory reconsolidation • Neural activation patterns differed during recent and remote fear memory reconsolidation. • The glutamatergic vCA1–BLA circuit strongly activated during US retrieval of remote fear memory. • Inhibiting vCA1–BLA circuit impaired reconsolidation of remote fear memory. • Activating vCA1–BLA circuit blocked the disruptive effect of propranolol on remote fear memory reconsolidation. Memory is retrieved and updated during reconsolidation, which provides a potential target for therapeutic intervention. Reconsolidation blockade following unconditioned stimulus (US) retrieval has shown increasing promise in disrupting persistent remote fear memory, yet the underlying neural mechanisms remain poorly understood. This study aims to elucidate the neural mechanisms involved in US retrieval-induced reconsolidation of remote fear memory. We established a rat model of contextual fear conditioning to investigate recent and remote fear memory with reconsolidation induced by US or conditioned stimulus (CS) retrieval. Pharmacological intervention, retrograde tracing, immunofluorescence, fiber photometry, as well as chemogenetic manipulation were employed to identify and manipulate key circuits involved in reconsolidation of fear memory. In this study, we show that pharmacological disruption of the US retrieval-induced reconsolidation of fear memory had a relatively long-lasting effect and was al...