The developing hippocampus undergoes profound structural and functional changes
that are critical for the establishment of functional networks. Disruptions in these
processes are implicated in a range of neurological and psychiatric disorders. Particular
attention is given to Cajal–Retzius cells, an early-born neuronal population with strong
synaptic integration into the hippocampus, whose dysfunction can be linked to impaired
memory and increased innate anxiety. The perspective then shifts to the maturation of
synaptic networks in the dentate gyrus, with a focus on granule cells and their perforant
path synapses as a key model of connectivity development. A multimodal approach
combining 3D electron microscopy, patch-clamp electrophysiology, and computational
simulations is used to uncover cellular and synaptic principles that shape hippocampal
development. During this period, synapses undergo profound structural changes that
may contribute to synaptic plasticity and enable memory formation within a functional,
mature hippocampal neural circuit.
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