Mu opioid receptors are in discrete hippocampal interneuron subpopulations

In the rat hippocampal formation, application of mu opioid receptor (MOR) agonists disinhibits principal cells, promoting excitation-dependent processes such as epileptogenesis and long-term potentiation. However, the precise location of MORs in particular inhibitory circuits, has not been determined, and the roles of MORs in endogenous functioning are unclear. To address these issues, the distribution of MOR-like immunoreactivity (-li) was examined in several populations of inhibitory hippocampal neurons in the CA1 region using light and electron microscopy. We found that MOR-li was present in many parvalbumin-containing basket cells, but absent from cholecystokinin-labeled basket cells. MOR-li was also commonly in interneurons containing somatostatin-li or neuropeptide Y-li that resembled the "oriens-lacunosum-moleculare" (O-LM) interneurons innervating pyramidal cell distal dendrites. Finally, MOR-li was in some vasoactive intestinal peptide- or calretinin-containing profiles resembling interneurons that primarily innervate other interneurons. These findings indicate that MOR-containing neurons form a neurochemically and functionally heterogeneous subset of hippocampal GABAergic neurons. MORs are most frequently on interneurons that are specialized to inhibit pyramidal cells, and are on a limited number of interneurons that target other interneurons. Moreover, the distribution of MORs to different neuronal types in several laminae, some relatively far from endogenous opioids, suggests normal functional roles that are different from the actions seen with exogenous agonists such as morphine.