The distribution of several neuropeptides (vasoactive intestinal polypeptide [VIP], cholecystokinin octapeptide [CCK], substance P [SP], neurotensin, methionine-enkephalin [Met-Enk] and somatostatin) in the hippocampal formation was studied with immunocytochemical techniques. Numerous VIP, CCK and somatostatin-positive cell bodies were found within the hippocampus and subiculum. Neurotensin-positive cell bodies were found within the subiculum, but no SP or Met-Enk-containing cell bodies were seen in either hippocampus proper or subiculum. VIP and CCK-positive cell bodies were predominantly located in the stratum moleculare and stratum radiatum of CA 1-2 regions and dentate gyrus, while somatostatin-containing cell bodies were found mainly in the stratum oriens. Nerve fibers containing each of the 6 peptides were found within the hippocampus. Large numbers of VIP, CCK and somatostatin fibers innervated the pyramidal and granule cell layers, with smaller numbers in the stratum radiatum and fewer still in the stratum molecular and stratum oriens. Other than a moderately dense neurotensin-positive fiber plexus in the dorsal subiculum, fewer neurotensin, SP and Met-Enk fibers were present. When present, these 3 peptides had a distribution restricted to a region close to the pyramidal layer in the Ca 2/3 region and to the stratum moleculare of the Ca 1 region. Peptide-containing fibers were identified entering or leaving the hippocampus in 3 ways, via the fornix (all 6 peptides), the dorsal subiculum (neurotensin-positive fibers projecting to the cingulate cortex: somatostatin, VIP and CCK present in fibers running between the dorsal subiculum and occipito-parietal cortex) and the ventral subiculum (VIP, CCK and somatostatin in fibers running between entorhinal cortex and hippocampus, and all 6 peptides in fibers crossing the amygdalo-hippocampal border). A major distinction exists between those peptides (VIP, CCK, somatostatin, neurotensin) which are found in cell bodies intrinsic to the hippocampal formation and those peptides (SP, Met-Enk) which are found only in hippocampal afferents. Differences were also noted between the connections of the dorsal hippocampus, which are predominant by way of the fornix and cingulate bundle, and the ventral hippocampus, which are with the entorhinal cortex and amygdala.
