Ultrastructural relationships between leu-enkephalin- and GABA-containing neurons differ within the hippocampal formation.

Electrophysiological studies have suggested that the excitatory actions of opioids in the hippocampal formation are mediated by inhibition of interneurons containing GABA; however, an anatomical basis for this interaction has never been established. Thus, we sought to determine the relationship between leu-enkephalin (LE)-containing axon terminals and GABAergic neurons using dual labeling immunohistochemistry and electron microscopy. In the CA1 region of the hippocampus, LE-labeled terminals (n = 99) were in direct contact with GABA-labeled perikarya and dendrites (18%), and directly apposed to GABA-labeled axon terminals (14%). In the molecular layer of the dentate gyrus, LE-containing terminals (n = 125) occasionally apposed GABA-containing terminals (8%). In the hilus of the dentate gyrus, LE-containing terminals (n = 165) often contacted GABA-containing perikarya and dendrites (39%), but rarely apposed GABA-containing terminals (3%). In the CA3 region of the hippocampus, only a few LE-labeled mossy fiber boutons (n = 102) contacted the shafts of GABA-labeled dendrites (4%). The results demonstrate that leu-enkephalin-containing terminals have a different anatomical relationship with GABA-containing profiles in each subregion of the hippocampal formation. In the CA1 region of the hippocampus, the data support the numerous electrophysiological studies indicating that LE functions in modulating inhibitory GABAergic neurons by both pre- and postsynaptic mechanisms. In the outer molecular layer of the dentate gyrus the localization suggests some presynaptic regulation of GABAergic terminals. In the hilus of the dentate gyrus, the study also supports the contention that LE may have an important role in regulating inhibition of GABA-containing neurons. In comparison, in the CA3 region of the hippocampus, LE may have a more limited role in regulating GABAergic inhibition by direct association.