Immunohistochemical localization of benzodiazepine/GABAA receptors in the human hippocampal formation.
Monoclonal antibodies to a purified benzodiazepine/GABAA receptor complex from bovine cerebral cortex were used to determine the localization of this receptor in immunohistochemical preparations of the human hippocampal formation. The regional localization of the receptor was compared with the autoradiographic distribution of binding sites for a benzodiazepine antagonist, Ro 15-1788, and very similar patterns were observed. The highest levels of labeling were present in the molecular layer of the dentate gyrus, where much of the immunoreaction product was localized on the dendrites of granule cells. Lower levels of staining were observed in the granule cell layer, where reaction product was distributed around the perimeter of granule cell somata. The staining patterns varied among the different fields of the hippocampus. Labeling was lowest in the CA3 field, increased somewhat in the CA2 field, and was highest in the CA1 field. Within CA1, a laminar pattern was observed. Moderate to high levels of staining were present in strata oriens, pyramidale, radiatum, and moleculare, whereas less staining was observed in stratum lacunosum. The cellular localization of the receptor also differed among the hippocampal fields. Very little reaction product was observed on pyramidal neurons in the CA3 field, but labeling of pyramidal neurons appeared to increase progressively throughout CA2, CA1, and the subiculum. Nonpyramidal neurons were prominently labeled in all hippocampal fields. These results indicate that the benzodiazepine/GABAA receptor is heterogeneously distributed among the different fields and on different neuronal cell types of the human hippocampus.
Houser
C R
CR
Neurology Service, Veterans Administration Medical Center, West Los Angeles, Wadsworth Division, California.
Olsen
R W
RW
Richards
J G
JG
Möhler
H
H
D000911:Antibodies, Monoclonal; D001345:Autoradiography; D005442:Flumazenil / Q000494:pharmacology; D006624:Hippocampus / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D007700:Kinetics; D011963:Receptors, GABA-A / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D011963:Receptors, GABA-A; D005442:Flumazenil