Light and electron microscopic substance P (SP) immunostaining was per
formed on hippocampal sections of colchicine-pretreated, control, untr
eated fimbria-fornix-transected (5 days), as well as perforant path-st
imulated Sprague-Dawley rats fixed in 5% acrolein. Numerous SP-immunor
eactive neurons could be observed in the stratum oriens of the Ammon's
horn and subiculum, fewer were seen in the dentate hilar area and str
atum radiatum of CA2 and CA3, and even fewer were seen at the border b
etween the CA1 strata radiatum and the lacunosum moleculare of CA1 sub
field. A higher dose of colchicine resulted in SP immunoreactivity in
a large population of granule cells and messy axon terminals. The enti
re CA2 region, the stratum oriens of CA1, CA3, and the subiculum were
densely innervated by SP-containing axon terminals. A homogeneous SP i
nnervation was found in the stratum radiatum of CA1. Only a few SP fib
ers were seen adjacent to the granule cell layer. Symmetric axosomatic
contacts were seen between SP-containing boutons and somata in the st
ratum oriens of the Ammon's horn. However, throughout the hippocampal
formation, the majority of SP-containing axons formed axodendritic sym
metric synapses. A dense population of SP-immunoreactive boutons that
formed axodendritic asymmetric synapses was observed in the strata ori
ens and radiatum of the CA3a and CA2 regions, and a few were found in
the supragranular and subgranular layers of the dentate gyrus. Fimbria
-fornix transection resulted in a marked loss of SP fibers in the stra
ta oriens, pyramidale, and radiatum of the CA3a and CA2 subfields. In
perforant pathway-stimulated animals, a population of granule cells an
d a large number of messy axon terminals were immunoreactive for SP. T
hese observations suggest two sources of SP innervation to the hippoca
mpal formation: one arising from intrinsic sources (interneurons and g
ranule cells) and one arising from extrinsic sources, most likely the
supramammillary region. (C) 1997 Wiley-Liss, Inc.