Hippocampal Cajal-Retzius cells receive inputs from several extrahippocampal areas

Cajal-Retzius (CR) cells are essential players in early brain development. In the first postnatal week (P0-P7), these glutamatergic cells densely populate the most superficial layer of the cerebral cortex, providing a transient source of excitatory inputs to immature pyramidal neurons. In the murine brain, CR cells are greatly reduced in the neocortex after postnatal week two, whereas in hippocampus, they persist throughout postnatal development and even into adulthood. During this time, they are integrated in the CA1 network, and recent work (Glærum et al. 2024) has showed that their persistence in the hippocampus is critical for the development of hippocampal circuitry. However, the extent of their connectivity remains poorly understood, hindering our appreciation of the role of these cells in postnatal development. In order to grasp the full extent of the CR cell’s network, it is imperative to identify the sources of input onto these cells, as well as which regions and cells they target. Thus, this project aims to examine the long-range projections to, and from, hippocampal CR cells. To achieve this, we are combining the use of transgenic mouse lines, viral vectors and state-of-the-art anatomical techniques, such as confocal and light-sheet microscopy. Preliminary results show that CR cells receive inputs from several extrahippocampal areas including entorhinal cortex, thalamus, and the midbrain. This points towards CR cells as an intermediate target of most, if not all, afferent fibers reaching the hippocampus during early development. Thus, CR cells likely play a critical role in the establishment of extrahippocampal connectivity.