Holistic Bursting Cells Store Long-term Memory in Auditory Cortex

Abstract The sensory neocortex has been since long suggested to be a substrate for long-term memory storage, yet which exact cells store long-term memories remained neither known nor visible over a century. Here, using a combination of day-by-day two-photon Ca2+ imaging and targeted single-cell loose-patch recording in a non-fear auditory associative learning paradigm, we reveal sparsely distributed neurons in layer 2/3 of auditory cortex emerged step-wise from quiescence into bursting mode, which then invariably expressed a holistic information of the learned composite sounds, referred to as holistic bursting (HB) cells. Notably, it was not shuffled populations but the same sparse HB cells that causally embodied the behavioral relevance of the learned composite sounds, pinpointing HB cells as long-term memory storage in the sensory neocortex.