Institute of Biomedical Innovation, Jiangxi Medical College, Nanchang University, Nanchang, China; Department of Rehabilitation Medicine, Huashan Hospital, State Key Laboratory of Medical Neurobiology, Institute for Translational Brain Research, MOE Frontiers Center for Brain Science, MOE Innovative Center for New Drug Development of Immune Inflammatory Diseases, Fudan University, Shanghai, China
Wenqu Yin
Institute of Biomedical Innovation, Jiangxi Medical College, Nanchang University, Nanchang, China
Xin Wang
Department of Rehabilitation Medicine, Huashan Hospital, State Key Laboratory of Medical Neurobiology, Institute for Translational Brain Research, MOE Frontiers Center for Brain Science, MOE Innovative Center for New Drug Development of Immune Inflammatory Diseases, Fudan University, Shanghai, China
Jiawen Li
Institute of Biomedical Innovation, Jiangxi Medical College, Nanchang University, Nanchang, China; The Second Clinical Medicine School of Nanchang University, Nanchang, China
Shanglin Zhou
State Key Laboratory of Medical Neurobiology, Institute for Translational Brain Research, MOEFrontiers Center for Brain Science, Fudan University, Shanghai, China
Chaolin Ma
Institute of Biomedical Innovation, Jiangxi Medical College, Nanchang University, Nanchang, China
Department of Rehabilitation Medicine, Huashan Hospital, State Key Laboratory of Medical Neurobiology, Institute for Translational Brain Research, MOE Frontiers Center for Brain Science, MOE Innovative Center for New Drug Development of Immune Inflammatory Diseases, Fudan University, Shanghai, China
Institute of Biomedical Innovation, Jiangxi Medical College, Nanchang University, Nanchang, China; Institute of Brain Science and Department of Physiology, School of Basic Medical Science, Hangzhou Normal University, Hangzhou, China
Time estimation is an essential prerequisite underlying various cognitive functions. Previous studies identified ‘sequential firing’ and ‘activity ramps’ as the primary neuron activity patterns in the medial frontal cortex (mPFC) that could convey information regarding time. However, the relationship between these patterns and the timing behavior has not been fully understood. In this study, we utilized in vivo calcium imaging of mPFC in rats performing a timing task. We observed cells that showed selective activation at trial start, end, or during the timing interval. By aligning long-term time-lapse datasets, we discovered that sequential patterns of time coding were stable over weeks, while cells coding for trial start or end showed constant dynamism. Furthermore, with a novel behavior design that allowed the animal to determine individual trial interval, we were able to demonstrate that real-time adjustment in the sequence procession speed closely tracked the trial-to-trial interval variations. And errors in the rats’ timing behavior can be primarily attributed to the premature ending of the time sequence. Together, our data suggest that sequential activity maybe a stable neural substrate that represents time under physiological conditions. Furthermore, our results imply the existence of a unique cell type in the mPFC that participates in the time-related sequences. Future characterization of this cell type could provide important insights in the neural mechanism of timing and related cognitive functions.
