KAPPA-OPIOID RECEPTOR-LIKE IMMUNOREACTIVITY IS PRESENT IN SUBSTANCE P-CONTAINING SUBCORTICAL AFFERENTS IN GUINEA-PIG DENTATE GYRUS

We have previously shown that kappa opioid receptor-like immunoreactiv ity (KT-LI) is present in axons and terminals in the granule cell laye r and inner molecular layer of the guinea pig dentate gyrus. The distr ibution and ultrastructural appearance of processes with KT-LI were si milar to those of the substance P (SP)-containing afferents which aris e from the supramammillary region of the hypothalamus (SUM) and enter the hippocampal formation through the fimbria-fornix. The objective of the present study was to determine whether the terminals with KT-LI a re likely to be SUM afferents. To accomplish this we 1) compared the i ntensity of KT- and SP-immunolabeling in the dentate gyrus ipsilateral and contralateral to a unilateral fornix transection and 2) used dual -labeling electron microscopy to determine whether terminals with KT-L I colocalize SP-LI in the dentate gyrus. Light microscopic examination of the dentate gyrus demonstrated that KT-LI and SP-LI were in thin p rocesses with overlapping distributions in strata granulosum and molec ulare. Following fornix transection, both KT-LI and SP-LI were dramati cally reduced in these regions of the dentate gyrus ipsilateral to the transection, consistent with an SUM origin. By electron microscopy, m ost (71%) terminals with KT-LI also contained detectable SP-LI in sing le-section analysis. Many dual-labeled terminals formed thick asymmetr ic synaptic contacts with large dendritic shafts (2-5 mu m) or granule cell perikarya, and a smaller proportion contacted dendritic spines; these characteristics resembled those of identified SUM afferents in o ther species. The demonstrations that 1) KT-LI colocalizes with SP-LI in a morphologically distinctive population of axon terminals and 2) m ost of the processes with KT-LI enter through the fimbria-fornix sugge st that kappa opioid receptors are present in the SUM projection to th e dentate gyrus. (C) 1997 Wiley-Liss, Inc.