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input associativity underlies fear memory renewal

National Science Review 2021年第9期8卷 121-136页

作者： Wei-Guang Li Yan-Jiao Wu Xue Gu Hui-Ran Fan Qi Wang Jia-Jie Zhu Xin Yi Qin Wang Qin Jiang Ying Li Ti-Fei Yuan Han Xu Jiangteng Lu Nan-Jie Xu Michael Xi Zhu Tian-Le Xu Center for Brain Science of Shanghai Children's Medical Center Shanghai Jiao Tong University School of Medicine Shanghai Key Laboratory of Psychotic Disorders Shanghai Mental Health Center Shanghai Jiao Tong University School of Medicine Center for Neuroscience and Department of Neurology of the Second Affiliated Hospital NHC and CAMS Key Laboratory of Medical Neurobiology Zhejiang University School of Medicine Department of Anatomy and Physiology Shanghai Jiao Tong University School of Medicine Shanghai Research Center for Brain Science and Brain-Inspired Intelligence Department of Integrative Biology and Pharmacology Mc Govern Medical School University of Texas Health Science Center at Houston

Synaptic associativity, a feature of Hebbian plasticity wherein coactivation of two inputs onto the same neuron produces synergistic actions on postsynaptic activity, is a primary cellular correlate of associative learning. However, whether and how synaptic associativity are implemented into context-dependent relapse of extinguished memory(i.e. fear renewal) is unknown. Here, using an auditory fear conditioning paradigm in mice, we show that fear renewal is determined by the associativity between convergent inputs from the auditory cortex(ACx) and ventral hippocampus(v HPC) onto the lateral amygdala(LA) that reactivate ensembles engaged during learning. Fear renewal enhances synaptic strengths of both ACx to LA and the previously unknown v HPC to LA monosynaptic inputs. While inactivating either of the afferents abolishes fear renewal, optogenetic activation of their input associativity in the LA recapitulates fear renewal. Thus, input associativity underlies fear memory renewal.

关键词： fear renewal memory ensembles input associativity long-term potentiation ventral hippocampus auditory cortex lateral amygdala

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