Postnatal persistence of hippocampal Cajal-Retzius cells has a critical role in the establishment of the hippocampal circuit.

Cajal-Retzius (CR) cells are a transient neuron type that populate the postnatal hippocampus. To understand how CR cells' persistence influences the maturation of hippocampal circuits, we combined a specific transgenic mouse line with viral vector injection to selectively ablate CR cells from the postnatal hippocampus. We observed layer-specific changes in the dendritic complexity and spine density of CA1 pyramidal cells. In addition, transcriptomic analysis highlighted significant changes in the expression of synaptic related genes across development. Finally, we were able to identify significant changes in the expression levels of Latrophilin-2, a postsynaptic guidance molecule known for its role in the entorhinal-hippocampal connectivity. Those findings were supported by changes in the synaptic proteomic content in CA1 stratum lacunosum-moleculare. Our results reveal a critical role of CR cells in the establishment of the hippocampal network.