Distribution of neurons and axons immunoreactive with antisera against neuropeptide Y in the normal human hippocampus.

The detailed distribution of neuropeptide tyrosine (neuropeptide Y; NPY) immunoreactive neurons and fibers is given for the normal human hippocampus. These neuronal elements are detected by a polyclonal antibody raised against the unconjugated peptide and controls were obtained by using liquid phase absorption immunocytochemistry. The description covers the distribution in the area dentata, the hippocampal subfields CA3 and CA1, the subicular complex, and the entorhinal area. Each region is distinct in its NPY content. In general, the hippocampal NPY immunoreactive neurons fall into distinct classes--large hilar neurons; cortical small bipolar or bitufted neurons; medium-sized multipolar neurons in the deep cortical layers; and finally the distinct, small bipolar NPY neurons of the white matter bundles. None of the NPY neurons are pyramidal; many are likely to be local circuit neurons, but some appear to have extrinsic connections. The NPY immunoreactive axonal innervation is dense throughout the hippocampus but shows distinct regional differences in the hippocampal subdivisions. The area dentata has hilar NPY immunoreactive neurons and radial varicose fibers scattered throughout without a clear laminar preference. Subfield CA3 is comparatively the weakest NPY-containing region and contrasts with CA1, which is well endowed with reactive neurons and a rich and unusual axonal innervation, with distinct laminar axonal specializations. The subicular complex is well endowed with cells and fibers and the parasubiculum consistently displays unusually heavy NPY innervation. The entorhinal area exhibits a rich cortical distribution pattern, like that previously described for the human cerebral cortex (Chan-Palay et al; J. Comp. Neurol. 238:382-390, '85a,b). The fimbria, alveus, and angular bundle have NPY neurons embedded within the white matter. Like the NPY immunoreactive innervation of the hippocampal regions of laboratory animals, the human NPY innervation seems to follow a common fundamental pattern with respect to cell locations, cell morphology, and axonal innervation. The difference, however, is the greater complexity and profusion of the NPY-immunoreactive axonal plexuses in the human hippocampus. This rich peptide network within the hippocampus with likely extrahippocampal interconnections raises questions concerning coexistence with other neuroactive substances, the functions of such substantial networks, and how they are altered in human neurological disease.