Contextual Fear Learning and Extinction in the Primary Visual Cortex of Mice
Xiaoke Xie1,2,3 · Shangyue Gong4 · Ning Sun5 · Jiazhu Zhu3,6 · Xiaobin Xu5 · Yongxian Xu5 · Xiaojing Li5 · Zhenhong Du3,6 · Xuanting Liu5 · Jianmin Zhang4 · Wei Gong4,5 · Ke Si1,2,3,5,6
1 Department of Psychiatry, The First Afliated Hospital, Zhejiang University School of Medicine, Hangzhou 310012, China
2 College of Biomedical Engineering and Instrument Science, Zhejiang University, Hangzhou 310012, China
3 Intelligent Optics & Photonics Research Center, Jiaxing Research Institute, Zhejiang University, Jiaxing 314001, China
4 Department of Neurosurgery of the Second Afliated Hospital, Zhejiang University School of Medicine, Hangzhou 310012, China
5 MOE Frontier Science Center for Brain Science & Brain-Machine Integration, NHC and CAMS Key Laboratory of Medical Neurobiology, School of Brain Science and Brain Medicine, Zhejiang University, Hangzhou 310012, China
6 State Key Laboratory of Modern Optical Instrumentation, College of Optical Science and Engineering, Zhejiang University, Hangzhou 310012, China
Abstract
Fear memory contextualization is critical for selecting adaptive behavior to survive. Contextual fear conditioning (CFC) is a classical model for elucidating related underlying neuronal circuits. The primary visual cortex (V1) is the primary cortical region for contextual visual inputs, but its role in CFC is poorly understood. Here, our experiments demonstrated that bilateral inactivation of V1 in mice impaired CFC retrieval, and both CFC learning and extinction increased the turnover rate of axonal boutons in V1. The frequency of neuronal Ca2+ activity decreased after CFC learning, while CFC extinction reversed the decrease and raised it to the naïve level. Contrary to control mice, the frequency of neuronal Ca2+ activity increased after CFC learning in microglia-depleted mice and was maintained after CFC extinction, indicating that microglial depletion alters CFC learning and the frequency response pattern of extinction-induced Ca2+ activity. These findings reveal a critical role of microglia in neocortical information processing in V1, and suggest potential approaches for cellular-based manipulation of acquired fear memory.
Keywords
Contextual fear conditioning; Calcium imaging; Primary visual cortex; Cortical plasticity; Microglial depletion; Learning and memory
