A long-standing model of the hippocampus’s role in memory needs to be revised, according to a new preprint. The network stores memories as synapses strengthen among coactivated cells, each encoding a different piece of the memory. The CA3 instead comprises two distinct types of pyramidal neurons arranged in two layers, with different morphology, physiology and connectivity patterns, the preprint suggests. A single transcription factor, ST18, distinguishes the two populations, the study reveals: A set of superficial CA3 neurons that express ST18 forms a recurrent network as predicted by the classical model, and a deeper set, which does not express ST18, regulates the superficial one. “I think it will transform how [the CA3] processes information and receive the inputs and integrate the inputs, it looks like [the two populations] could be playing different roles.”