1. Academic Validation
  2. Dynamic redistribution of AMPA receptors toward memory-related neuronal ensembles in mice barrel cortex during sensory learning

Dynamic redistribution of AMPA receptors toward memory-related neuronal ensembles in mice barrel cortex during sensory learning

  • Neuron. 2025 Jul 2:S0896-6273(25)00433-7. doi: 10.1016/j.neuron.2025.06.002.
Junzhao Li 1 Rubing Zhou 2 Jinpeng Wang 1 Xiaochen Zhang 3 Yongfeng Li 1 Chuanyu Edward Li 1 Bin He 1 Chenyang Li 1 Changying Li 1 Shuai Long 1 Kongjie Lu 1 Zhaodi Liu 1 Rong Zhang 4 Chen Zhang 5 Yong Zhang 6
Affiliations

Affiliations

  • 1 Neuroscience Research Institute and Department of Neurobiology, School of Basic Medical Sciences, Peking University, Key Laboratory for Neuroscience, Ministry of Education of China and National Health Commission of the People's Republic of China, Beijing 100083, China; PKU-IDG/McGovern Institute for Brain Research, Beijing 100871, China.
  • 2 Department of Orthopaedics, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China.
  • 3 Academy of Medical Engineering and Translational Medicine, Tianjin University, Tianjin 300072, China.
  • 4 Neuroscience Research Institute and Department of Neurobiology, School of Basic Medical Sciences, Peking University, Key Laboratory for Neuroscience, Ministry of Education of China and National Health Commission of the People's Republic of China, Beijing 100083, China.
  • 5 School of Basic Medical Sciences, Beijing Key Laboratory of Neural Regeneration and Repair, Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing 100069, China.
  • 6 Neuroscience Research Institute and Department of Neurobiology, School of Basic Medical Sciences, Peking University, Key Laboratory for Neuroscience, Ministry of Education of China and National Health Commission of the People's Republic of China, Beijing 100083, China; PKU-IDG/McGovern Institute for Brain Research, Beijing 100871, China. Electronic address: yongzhang@hsc.pku.edu.cn.
Abstract

Understanding the dynamic processes of sensory learning and memory is essential for comprehending cognitive function. How neurons undergo synaptic changes at the receptor level in vivo to form a memory engram remains unclear. Here, we employed a genetic approach and identified memory-related (Robust Activity Marking [RAM+]) neuronal ensembles in the barrel cortex following a sensory detection task. Manipulation of RAM+ neurons replicated licking behavior, demonstrating their role in memory encoding. We observed a layer-selective activation pattern during learning with L2/3 excitatory neurons as primary targets. Two-photon in vivo imaging revealed distinct changes in spine surface GluA1 in L2/3 RAM+ and RAM- neurons during learning; both correlate with learning performance. Furthermore, connections between L4 and L2/3 RAM+ neurons were selectively strengthened during learning. Together, these results reveal a learning-induced α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) redistribution toward active neuronal ensembles in a layer-selective manner, which advances our understanding of cellular and synaptic mechanisms underlying sensory memory formation.

Keywords

AMPARs; barrel cortex; memory engram; sensory learning; synaptic plasticity; two-photon imaging.

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