Cajal-Retzius cells (CRs) are transient neurons, disappearing almost completely in the postnatal neocortex by programmed cell death (PCD), with a percentage surviving up to adulthood in the hippocampus. Here, we evaluate CR’s role in the establishment of adult neuronal and cognitive function using a mouse model preventing Bax-dependent PCD. CRs abnormal survival resulted in impairment of hippocampus-dependent memory, associated in vivo with attenuated theta oscillations and enhanced gamma activity in the dorsal CA1. At the cellular level, we observed transient changes in the number of NPY cells and altered CA1 pyramidal cell spine density. At the synaptic level, these changes translated into enhanced inhibitory currents in hippocampal pyramidal cells. Finally, adult mutants displayed an increased susceptibility to lethal tonic-clonic seizures in a kainate model of epilepsy. Our data reveal that aberrant survival of a small proportion of postnatal hippocampal CRs results in cognitive deficits and epilepsy-prone phenotypes in adulthood.We thank Dr. P. Billuart for critical reading of the manuscript and suggestions during the course of the study, the NeuroImag platform at the IPNP and SFR Necker Imaging and histology platforms at the Imagine Institute for help with acquisition, the animal house facility (LEAT) and Animalliance for animal care. We are grateful to N. Ramezanidoraki and P. Billuart for initiating the first MEA experiment as well as members of the Pierani’s lab for technical support and helpful discussions.We thank Ann Kennedy for mouse profile (Zenodo, 2020) doi:10.5281/zenodo.3925921and for the mouse scheme in Fig. 3a, French Ministry of Research (BioSPc Doctoral school) (M.R.), Fondation pour la recherche médicale, FDT20201201037 (M.R.), Centre national de la
recherche scientifique (CNRS) (A.P.), Agence Nationale de la Recherche, ANR-15-CE16-0003-01, ANR-19-CE16-0017-03 and ANR20-CE16-0001-01 (A.P.), Fondation pour la recherche médicale, Équipe FRM DEQ20130326521 and EQU201903007836) (A.P.), Agence Nationale de la Recherche under “Investissements d’avenir” program, ANR10-IAHU-01) (Imagine Institute), Fondation pour la recherche médicale (F.O.), AGEMED-INSERM (F.O.), NRJ for Neuroscience (F.O.), European Research Council (Consolidator grant #683154) (N. Rouach), European Research Council (Starting Grant #678250) (N. Rebola), Agence Nationale de la Recherche ANR-21-CE16-0020 and ANR-20-CE16-0009 (N. Rebola), and ANR-21-NEU2-0007-01 Eranet-Neuron ROSSINI project (A.P. and L.M.d.l.P.)
