title: Kappa opioid receptor-like immunoreactivity is present in substance P-containing subcortical afferents in guinea pig dentate gyrus.
abstract: We have previously shown that kappa opioid receptor-like immunoreactivity (KT-LI) is present in axons and terminals in the granule cell layer and inner molecular layer of the guinea pig dentate gyrus. The distribution and ultrastructural appearance of processes with KT-LI were similar to those of the substance P (SP)-containing afferents which arise 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 are likely to be SUM afferents. To accomplish this we 1) compared the intensity 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-LI colocalize SP-LI in the dentate gyrus. Light microscopic examination of the dentate gyrus demonstrated that KT-LI and SP-LI were in thin processes with overlapping distributions in strata granulosum and moleculare. Following fornix transection, both KT-LI and SP-LI were dramatically reduced in these regions of the dentate gyrus ipsilateral to the transection, consistent with an SUM origin. By electron microscopy, most (71%) terminals with KT-LI also contained detectable SP-LI in single-section analysis. Many dual-labeled terminals formed thick asymmetric synaptic contacts with large dendritic shafts (2-5 microns) or granule cell perikarya, and a smaller proportion contacted dendritic spines; these characteristics resembled those of identified SUM afferents in other species. The demonstrations that 1) KT-LI colocalizes with SP-LI in a morphologically distinctive population of axon terminals and 2) most of the processes with KT-LI enter through the fimbria-fornix suggest that kappa opioid receptors are present in the SUM projection to the dentate gyrus.
authors.affiliation: Department of Neurology and Neuroscience, Cornell University Medical College, New York, New York 10021, USA.
authors.forename: C T
authors.initials: CT
authors.lastname: Drake
authors.forename: C
authors.initials: C
authors.lastname: Chavkin
authors.forename: T A
authors.initials: TA
authors.lastname: Milner
mesh_terms: D000344:Afferent Pathways / Q000166:cytology* / Q000502:physiology; D000818:Animals; D001369:Axons / Q000648:ultrastructure*; D018891:Dentate Gyrus / Q000166:cytology* / Q000502:physiology*; D007839:Functional Laterality; D006168:Guinea Pigs; D007031:Hypothalamus / Q000166:cytology* / Q000502:physiology; D007150:Immunohistochemistry; D008297:Male; D016253:Microscopy, Immunoelectron; D009411:Nerve Endings / Q000648:ultrastructure*; D017473:Receptors, Opioid, kappa / Q000032:analysis*; D013373:Substance P / Q000032:analysis*; D013569:Synapses / Q000648:ultrastructure
chemical_list: D017473:Receptors, Opioid, kappa; D013373:Substance P