Zonal distribution of perforant path cells in layer III of the entorhinal area projecting to CA1 and subiculum in the rat

The distribution pattern of the cells that give rise to perforant path projections, including direct entorhino-CA1 and entorhino-subicular projections, was investigated in layer III of the medial and lateral entorhinal areas in the rat using retrograde labeling with horseradish peroxidase conjugated to wheat germ agglutinin and cholera toxin B subunit. Using two-dimensional unfolded maps of the entire hippocampal and parahippocampal fields, we found that cells projecting to a certain septotemporal level of CA1 and the subiculum were distributed in a band-like zone extending across the medial and lateral entorhinal areas. The transverse axis of these zones was disposed parallel to the rhinal fissure and their longitudinal axis was perpendicular to the boundary between the medial and lateral entorhinal areas. Projections to the septal CA1 originated from the zone near the rhinal fissure, whereas those to the temporal CA1 originated from the zone far from the rhinal fissure. Each zone in both the medial and lateral entorhinal areas involved many neurons projecting to a wide proximodistal range of CA1 and the subiculum. These results suggest that the entorhino-CA1 and entorhino-subicular perforant path projections are generally organized in a band-like zonal fashion with a gradient, rather than a point-to-point topographic arrangement.

► CA1 projection cells in layer III of the entorhinal area are distributed like a band.
► The entorhino-subicular projection cells are also arranged in a band-like pattern.
► The long axis of the bands was perpendicular to the medial/lateral entorhinal border.
► Each band involved cells innervating a wide proximodistal range of the hippocampus.
► Topographic manner of entorhino-hippocampal projections is graded within each band.