Development of the noradrenergic innervation of neocortex.

The development of the noradrenaline (NA)-neuron innervation of rat neocortex was studied by fluorescence histochemistry, high affinity uptake of [3H-]NA, and biochemical assay of regional NA content. Fluorescence histochemistry indicates that NA axons enter areas of developing neocortex prenatally and the innervation matures rapidly during early postnatal life. Frontal and lateral neocortical areas are the first to be innervated followed by occipital and parietal areas. All cortical layers receive innervation. The distribution and density of neocortical NA innervation achieves the adult pattern by the end of the first postnatal week. High affinity uptake studies confirm the observations from fluorescence histochemistry and show a very rapid maturation of the NA axon innervation with adult levels of uptake occurring by postnatal day 9. Following birth, there is a brief rise in NA content from PO to P2 in all neocortical areas. NA content then drops to low levels in all areas by P4. This is followed by a gradual increase in NA content in all areas occuring over several months. This pattern of development of NA axon innervation of neocortex demonstrates that the density and distribution of NA axons in developing neocortex matures much earlier than shown in previous studies whereas the NA content of the developing axonal plexus achieves adult levels later in postnatal life.