Hippocampal Development

This intriguing part of the cerebral cortex was one of the first structures we studied, so papers range in publication from the 1960s to the 1990s. We did not include this work in the NEOCORTICAL DEVELOPMENT book because the hippocampus is archicortex, not neocortex (NC in photo at right). The hippocampus is a limbic system structure in the mammalian telencephalon concerned with exploratory behavior and attention; other studies link it to memory and spatial awareness. The major components of the hippocampal region are the hippocampus proper: Ammon’s horn [CA1, CA3] and the dentate gyrus [DG].  The subiculum (SU), presubiculum (PR), parasubiculum (PA), and the entorhinal cortex (EC) are other structures in the region. Our studies include its embryology, neurogenetic timetables, behavioral modifications after X-irradiation to remove dentate granule cells (see hippocampus and behavior page), and many adult neurogenesis studies (see the adult neurogenesis page).

Our brief communication shows that the immature hippocampus in children is a likely active zone for postnatal neurogenesis in the dentate granular layer, indicating that our findings in rats can be applied to humans.


The Hippocampal Region in a Horizontal Section (P60 Normal Rat)

From Bayer 1980 (1)


It was while we were doing this analysis that we realized multiple injections of 3H-thymidine could be used to exactly determine the proportion of neurons generated on either single or multiple days.  We called it the “progressively-delayed cumulative labeling technique” (Bayer and Altman, 1974). The full explanation of that method can be found on the neocortical development page in the Appendix of the Neocortical Development book.  That method unlocked our ability to find neurogenetic gradients during brain development.  Most of these gradients can be linked to the pattern of topographic anatomical projections.
In the 4 photos above (From Bayer and Altman, 1974) the “top-down” neurogenetic gradient is easily discernable in the dentate granular layer after sequential injections of 3H-thymidine.

  1. labeled cells after 4 consecutive  injections on P0 (birth) to P3;
  2. injections P4 to P7;
  3. injections P12 to P15;
  4. injections P16 to P19.
The diagram to the right shows just one of many examples of the links we have found between the directions in neurogenetic gradients and the pattern of anatomical connections between brain structures.  The lateral septal nucleus and the mammillary body are the chief subcortical targets of topographically projecting axons from the pyramidal cells in Ammon’s horn of the hippocampus. Dorsal pyramidal cells innervate medial parts of the lateral septal nucleus and dorsal parts of the pars posterior of the mammillary body.  Ventral pyramidal cells innervate lateral parts of the lateral septal nucleus and ventral parts of the pars posterior of the mammillary body.  Ammon’s horn pyramidal cells are generated simultaneously in dorsal and ventral parts but dorsal pyramidal cells are nearer to their targets than ventral pyramidal cells.  Here is how the structures are linked:  Dorsal pyramidal cells with shorter axons (earlier arriving)innervate OLDER neurons in each target, while ventral pyramidal cells with longer axons (later arriving) innervate YOUNGER neurons in each target.
The general hypothesis we have formulated based on many correlations like these is: neurons are generated in exact sequences so that their axons and dendrites are available for innervation in the right times and places in the developing brain.  Thus, the complex anatomical connections between parts of the adult nervous system are laid down during rigidly timed developmental events.