Departments of Neuroscience and Biomedical Sciences, City University of Hong Kong, Hong Kong, China; Centre for Regenerative Medicine and Health, Hong Kong Institute of Science & Innovation, Chinese Academy of Sciences, Hong Kong SAR, China
Junfeng Su
Departments of Neuroscience and Biomedical Sciences, City University of Hong Kong, Hong Kong, China; City University of Hong Kong Shenzhen Research Institute, Shenzhen, Guangzhou, China
Wei Fang
Departments of Neuroscience and Biomedical Sciences, City University of Hong Kong, Hong Kong, China
Departments of Neuroscience and Biomedical Sciences, City University of Hong Kong, Hong Kong, China; City University of Hong Kong Shenzhen Research Institute, Shenzhen, Guangzhou, China
Departments of Neuroscience and Biomedical Sciences, City University of Hong Kong, Hong Kong, China; City University of Hong Kong Shenzhen Research Institute, Shenzhen, Guangzhou, China
Although fear memory formation is essential for survival and fear-related mental disorders, the neural circuitry and mechanism are incompletely understood. Here, we utilized trace fear conditioning to study the formation of trace fear memory in mice. We identified the entorhinal cortex (EC) as a critical component of sensory signaling to the amygdala. We adopted both loss-of-function and gain-of-function experiments to demonstrate that release of the cholecystokinin (CCK) from the EC is required for trace fear memory formation. We discovered that CCK-positive neurons project from the EC to the lateral nuclei of the amygdala (LA), and inhibition of CCK-dependent signaling in the EC prevented long-term potentiation of the auditory response in the LA and formation of trace fear memory. In summary, high-frequency activation of EC neurons triggers the release of CCK in their projection terminals in the LA, potentiating auditory response in LA neurons. The neural plasticity in the LA leads to trace fear memory formation.
