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

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.