Developmentally defined subcircuits in the hippocampus support spatial learning

Hippocampal circuits are composed of cells that exhibit heterogeneity in gene expression, connectivity, and intrinsic properties. This diversity arises during embryonic development, which produces parallel subcircuits along the trisynaptic pathway. To examine how these subcircuits support spatial memory, we combined embryonic birthdating of interconnected CA3-CA1 neurons with electrophysiology in a place-reward association task. Learning reorganized correlation patterns near rewarded locations, which were reactivated during sleep and predicted memory retrieval. Neurons born on the same day exhibited correlated activity across brain states and hippocampal subfields. Throughout learning, same-birthdate CA1 neurons coordinated their activity to encode the rewarded locations, but CA3 cells did not. These regional differences were mirrored by distinct patterns of connectivity between same-birthdate pyramidal cells and inhibitory interneurons. In particular, same-birthdate neurons converged onto parvalbumin-expressing CA1 interneurons, which were modulated by spatial learning. Together, our results demonstrate that development-defined subcircuits in the hippocampus are preconfigured to encode new memories.