title: In vivo imaging of immediate early gene expression reveals layer-specific memory traces in the mammalian brain.
abstract: The dynamic processes of formatting long-term memory traces in the cortex are poorly understood. The investigation of these processes requires measurements of task-evoked neuronal activities from large numbers of neurons over many days. Here, we present a two-photon imaging-based system to track event-related neuronal activity in thousands of neurons through the quantitative measurement of EGFP proteins expressed under the control of the EGR1 gene promoter. A recognition algorithm was developed to detect GFP-positive neurons in multiple cortical volumes and thereby to allow the reproducible tracking of 4,000 neurons in each volume for 2 mo. The analysis revealed a context-specific response in sparse layer II neurons. The context-evoked response gradually increased during several days of training and was maintained 1 mo later. The formed traces were specifically activated by the training context and were linearly correlated with the behavioral response. Neuronal assemblies that responded to specific contexts were largely separated, indicating the sparse coding of memory-related traces in the layer II cortical circuit.
authors.affiliation: Ministry of Key Laboratory of Protein Sciences, Tsinghua-Peking Joint Center for Life Sciences, Center for Epigenetics and Chromatin Biology, School of Life Sciences, Tsinghua University, Beijing 100084, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Xie
authors.forename: Yu
authors.initials: Y
authors.lastname: Liu
authors.forename: Youzhi
authors.initials: Y
authors.lastname: Zhu
authors.forename: Xinlu
authors.initials: X
authors.lastname: Ding
authors.forename: Yuhao
authors.initials: Y
authors.lastname: Yang
authors.forename: Ji-Song
authors.initials: JS
authors.lastname: Guan
mesh_terms: D000818:Animals; D001931:Brain Mapping / Q000379:methods*; D002540:Cerebral Cortex / Q000166:cytology* / Q000502:physiology; D015870:Gene Expression / Q000502:physiology*; D017781:Genes, Immediate-Early / Q000235:genetics / Q000502:physiology*; D049452:Green Fluorescent Proteins / Q000378:metabolism; D007091:Image Processing, Computer-Assisted; D057567:Memory, Long-Term / Q000502:physiology*; D051379:Mice; D008856:Microscopy, Fluorescence; D009474:Neurons / Q000378:metabolism / Q000502:physiology*
chemical_list: C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins