Summary

A bioRxiv preprint reports that hippocampal Cajal-Retzius cells receive traced input from at least seven areas outside the hippocampus. The authors also describe strychnine-sensitive activity and close positioning of entorhinal fibres to glycinergic receptors.

A bioRxiv preprint by Kristian Moan and Giulia Quattrocolo reports that hippocampal Cajal-Retzius cells receive input from at least seven brain areas outside the hippocampus. The authors also found that part of these cells’ spontaneous activity is strychnine-sensitive, alongside anatomical evidence placing fibres from the entorhinal cortex near glycinergic receptors on the cells.

A wider set of inputs to a persistent cell population

Cajal-Retzius cells are early-born neurons involved in embryonic brain development. Most undergo programmed cell death after birth, but a population in the hippocampus persists into adulthood. These hippocampal Cajal-Retzius cells, abbreviated hCR cells, have been implicated in the arrival of entorhinal connections and the development of hippocampal circuits.

The preprint uses transsynaptic rabies tracing to identify inputs to hCR cells. The authors report input from at least seven extrahippocampal areas, whose source populations they describe as putatively glutamatergic. Before this work, the abstract notes, only local GABAergic synaptic input had been demonstrated onto hCR cells.

Pharmacological and anatomical clues

The authors report that a portion of hCR cells’ spontaneous activity is sensitive to strychnine. They also describe fibres from layer II of the entorhinal cortex positioned within 300 nanometres of glycinergic receptors on hCR cells. This close apposition is an anatomical observation; the preprint’s proposed interpretation is that hCR cells may receive long-range input through atypical receptor signalling.

The findings broaden the proposed role of hCR cells: rather than interacting only with local inputs, they may help guide multiple afferent pathways terminating in the hippocampus. The authors suggest that this could contribute to hippocampal maturation. The reported pharmacological sensitivity and receptor proximity offer complementary clues, while leaving the precise functional link between the traced projections and the cells’ activity to be characterised.

The work is a bioRxiv preprint. Its abstract does not give the species, sample sizes or quantitative effect estimates, so the findings should be read as an early account of the proposed circuit and signalling mechanism.

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