Distribution and morphology of serotonin-immunoreactive axons in the hippocampal region of the New Zealand white rabbit. I. Area dentata and hippocampus.

This study provides a detailed light microscopic description of the morphology and distribution of immunohistochemically stained serotonergic axons in the hippocampal region of the New Zealand white rabbit. The serotonergic axons were segregated morphologically into three types: beaded fibers, fine fibers, and stem-axons, respectively. Beaded fibers were thin serotonergic axons with large varicosities, whereas thin axons with small fusiform or granular varicosities were called fine fibers. Finally, thick straight non-varicose axons were called stem-axons. Beaded fibers often formed large conglomerates with numerous boutons (pericellular arrays) in close apposition to the cell-rich layers in the hippocampal region, e.g., the granular and hilar cell layers of the dentate area and the pyramidal cell layer ventrally in CA3. The pericellular arrays in these layers were often encountered in relation to small calbindin-D2BK-positive cells, as shown by immunohistochemical double staining for serotonin and calbindin-D28K. The beaded and fine serotonergic fibers displayed a specific innervation pattern in the hippocampal region and were encountered predominantly within the terminal field of the perforant path, e.g., the stratum moleculare hippocampi and the outer two-thirds of the dentate molecular layer. These fibers were also frequently seen in the deep part of the stratum oriens and the alveus, forming a dense plexus in relation to large multipolar calbindin-D28K-positive cells and their basal extensions. Stem-axons were primarily seen in the fimbria and alveus. This innervation pattern was present throughout the entire hippocampal formation, but there were considerable septotemporal differences in the density of the serotonergic innervation. A high density of innervation prevailed in the ventral/temporal part of the hippocampal formation, whereas the dorsal/septal part received only a moderate to weak serotonergic innervation. These results suggest that the serotonergic system could modulate the internal hippocampal circuitry by way of its innervation in the terminal field of the perforant path, the hilus fasciae dentatae, and ventrally in the zone closely apposed to the mossy fiber layer and the pyramidal cells of CA3. This modulation could be of a dual nature, mediated directly by single serotonergic fibers traversing the hippocampal layers or indirectly by the pericellular arrays and their close relation to the calbindin-D28K-positive cells. The marked septotemporal differences in innervation density point toward a difference between the ventral and dorsal parts of the hippocampal formation with respect to serotonergic function and need for serotonergic modulation.