Moan, K. | Search bioRxiv

bioRxiv2026

Spatial representation in CA1 superficial pyramidal cells is impaired after postnatal ablation of hippocampal Cajal Retzius cells

Cajal-Retzius neurons (CRs) are a transient cell type that populates the postnatal hippocampus. To test how the persistence of CRs shapes the maturation of hippocampal function, we used a CRs-specific transgenic mouse line combined with targeted viral delivery to selectively ablate CRs in the postnatal hippocampus. Single cell sequencing revealed that gene networks in superficial CA1 pyramidal cells were more strongly perturbed compared to deep CA1 pyramidal cells. To test if these two subpopulations were also distinctly affected in their function, we performed in vivo recordings from spatially modulated cells in CA1. Our analysis showed an impaired spatial representation specifically in superficial CA1 pyramidal cells. Additionally, we observed an increased CA3 to CA1 excitatory drive, as indicated by increased gamma oscillations, and alterations of intrinsic firing properties in superficial CA1 pyramidal neurons confirmed by in vitro electrophysiological recordings. Together, these results indicate a crucial role for CRs in the maturation of hippocampal subcircuits.

neuroscience↗

bioRxiv2025

Differences in Cajal-Retzius cell density and postnatal persistence across cortical areas revealed by a novel intersectional genetic labeling approach

Cajal-Retzius (CR) cells are glutamatergic neurons that transiently populate the most superficial layer of the isocortex and allocortex during development, serving an essential role during both prenatal and early postnatal brain development. Notably, these cells disappear from most cortical areas by postnatal day 14, but persist for much longer in the hippocampus. We developed a novel intersectional genetic labeling approach for CR cells that captures almost all of the TRP73-positive CR cells throughout the isocortex and allocortex. This intersectional strategy offers several advantages over previous methods commonly used for CR cell targeting. Here, we applied this new CR cell labeling strategy to investigate the distribution and persistence of CR cells throughout the whole mouse brain, at four different postnatal ages. We observed that the initial CR cell density and the rate of their disappearance varies substantially across different brain areas during development. Strikingly, we observed variation in cell death rate even between adjacent cortical subregions: comparing the medial and the lateral entorhinal cortex, the former retains a high density of CR cells for several months in contrast to the latter. Our results present a necessary revision of the phenomenon of CR cell persistence, showing that, in addition to hippocampus, several other cortical areas maintain a high density of these cells beyond the first two postnatal weeks.

neuroscience↗