Ontogeny of the noradrenergic innervation of the rat hippocampal formation.

The noradrenergic (NA) innervation of the rat hippocampal formation arrives embryonically into a structure in which cytogenesis and cell migration are still active processes. At embryonic day 18 (E18) the first fluorescent axons appear in the septal end of CA3 at the boundary of the marginal zone and cortical plate, the future stratum lucidum. By birth axons invade the subiculum and also course along the septo-temporal axis in a longitudinal associational system in stratum moleculare of CA3. The innervation of the area dentata increases significantly by postnatal day four (P4). The innervation pattern throughout the dentate and Ammon's horn is fairly complete by P10. High affinity uptake of 3H-NA also matures embryonically and correlates postnatally with the extent of innervation estimated by fluorescence histochemistry. The levels of endogenous NA develop more slowly, showing only 60--80% of older adult values by P48. Compared to the maturation of other hippocampal afferents, the NA innervation is extremely precocious. It is localized in areas which could allow it to have significant trophic functions during early stages of histogenesis. In addition, its presence in the rapidly developing structure may contribute to its eventual distribution in a relatively less organized terminal pattern than that of the later-arriving entorhinal, commissural and septal afferents.