Subicular-parahippocampal projections revisited: development of a complex topography in the rat.

The subicular-parahippocampal projection has been proposed as the major output pathway of the hippocampus. This projection shows a striking topographic organization along its three-dimensional axes. Here we aimed to study the development of this projection system. We found that an adult-like topography of subiculum-to-parahippocampal projections is present by postnatal day 7 (P7). The cellular morphology in the subiculum is immature at this age, reaching maturity by P15-19. The density of projections increases from P7 to P15-19 but does so within the constraints of the adult topography. Projections to the entorhinal cortex show a clear arrangement in line with the adult data, in that distal portions of the subiculum project to the medial entorhinal cortex, whereas proximal portions project to the lateral entorhinal cortex. Our results add new details to the proximodistal organization of projections to the pre- and parasubiculum. We show that these projections arise exclusively from the more distal part, sharing their origin with that of medial entorhinal projections. Within this distal portion of the subiculum, a proximodistal gradient of origin maps onto a presubicular termination gradient starting in proximal presubiculum and extending gradually until it covers the proximodistal extent. Proximally located neurons in the distal part of the subiculum target the distal portion of the parasubiculum, and distal subicular neurons target the proximal most portion of parasubiculum. Given the specificity of the known topographic projections this early in development, we expect that these newly described topographic features will be maintained in the adult.