Aberrant survival of hippocampal Cajal-Retzius cells leads to memory deficits, gamma rhythmopathies and susceptibility to seizures in adult mice

Martina Riva, Stéphanie Moriceau, Annunziato Morabito, Elena Dossi, Candela Sanchez-Bellot, Patrick Azzam, Andrea Navas-Olive, Beatriz Gal, Francesco Dori, Elena Cid, Fanny Ledonne, Sabrina David, Fabrice Trovero, Magali Bartolomucci, Eva Coppola, Nelson Rebola, Antoine Depaulis, Nathalie Rouach, Liset Menendez de la Prida, Franck Oury, Alessandra Pierani

Source : Nat Commun

2023 Mar 18

Pmid / DOI: 36934089


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.

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