Long-Range Glutamatergic Projections Target Hippocampal Cajal-Retzius Cells Through Atypical Receptor Signaling

Abstract

Cajal-Retzius (CR) cells are a population of early-born, transient neurons that serve an indispensable role during embryonic brain development. Postnatally, most CR cells undergo programmed cell-death, except in a few areas, including the hippocampus, where they persist until adulthood. The hippocampal population of CR (hCR) cells have previously been implicated in receiving and facilitating ingrowth of entorhinal afferents and the establishment of the hippocampal circuit. Nevertheless, only local GABAergic synaptic input has been demonstrated onto hCR cells before. Through transsynaptic rabies tracing we show that hCR cells receive input for at least seven extrahippocampal areas, all putative glutamatergic populations, even though CR cell spontaneous activity is speculated to be exclusively mediated through GABAergic action. Here, we show that a portion of CR cell spontaneous activity is strychnine-sensitive, and that glutamatergic fibers from entorhinal cortex layer II apposition themselves in physiological distance (<300 nm) to glycinergic receptors on hCR cells. We propose that hCR cells guide several, if not all, afferents terminating in stratum lacunosum moleculare and the outer molecular layer in the hippocampus. These findings shine new light on how hCR cells might facilitate hippocampal maturation.