Localization and development of nerve growth factor-sensitive rat basal forebrain neurons and their afferent projections to hippocampus and neocortex.

In order to understand further the role of NGF in the development of NGF-sensitive basal forebrain neurons and their afferent connections to the hippocampus and neocortex, we have used monoclonal antibody 192 IgG to detect and localize NGF receptors immunocytochemically in the developing rat brain. NGF receptor immunoreactivity (NGF-RI) is first visible at embryonic day 13 (E 13) in the ventrolateral telencephalic wall and follows a caudal-to-rostral gradient in its initial appearance. NGF-RI neuronal number and neuropil staining undergo substantial increases before birth, and extensive dendritic growth and increases in perikaryal size continue during the first 3 weeks of postnatal life. This growth and cellular differentiation, however, is followed in the fourth postnatal week and later by an apparent decrease in dendritic arborization and 50% shrinkage in the size of perikarya. Initial NGF-RI fiber outgrowth from immature basal forebrain neurons directed toward appropriate target fields is observed as early as E 15. The formation of a laminar pattern by septal axons in the hippocampal terminal fields and invasion of NB afferents into the cortex occur postnatally over a protracted time. In the hippocampus, NGF-RI is initially diffusely distributed, and wide bands of immature granule and pyramidal cells are almost devoid of immunoreactive fibers; however, with maturity, septal axon terminals become concentrated in narrow zones closely associated with the cellular layers. In the neocortex, early-arriving basal forebrain afferents accumulate in the intermediate zone underneath the darkly immunoreactive subplate before they enter The cortex. Dense subplate and transiently present, radially aligned fiber staining completely disappear in later postnatal week and are gradually replaced by specific axonal and terminal staining associated with NB afferents. The expression of NGF receptor in the subplate zone at the time afferents arrive and its subsequent disappearance with the specific terminal formation suggest that NGF receptor and concomitant accumulation of NGF in the subplate may act as a temporary target for the early-arriving basal forebrain afferents; ingrowing afferents may then be guided by radially oriented NGF-RI fibers to proper synaptic sites.