Neuronal types expressing μ- and δ-opioid receptor mRNA in the rat hippocampal formation

Opioids are thought to control the excitability of hippocampal principal neurons indirectly by inhibiting GABAergic interneurons. However, direct inhibition of hippocampal principal neurons by opioids has also been reported. To understand better the neuromodulatory role of opioids in rat hippocampal circuits, we analyzed types of mu- and delta-opioid receptor (MOR, DOR)-expressing hippocampal neurons. Most MOR-immunoreactive neurons in the granular and pyramidal cell layers exhibited multipolar morphologies characteristic of GABAergic neurons. Virtually all neurons in the hippocampal formation expressing high MOR mRNA levels cocontained the mRNA for glutamic acid decarboxylase (GAD). Most parvalbumin-, several calretinin-, and several pre-proenkephalin-containing neurons expressed the MOR gene in the hippocampal formation. Expression of high DOR mRNA levels was restricted to GAD-positive neurons in the principal cell layers, oriens layer and hilus. More than 90% of the parvalbumin-positive neurons in the hippocampal formation strongly expressed the DOR gene. Granule cells expressing vesicular glutamate transporter 1 (VGLUT1) mRNA contained very low MOR and DOR transcript levels. In VGLUT1-positive pyramidal cells, weak DOR but no MOR gene expression was detected. Whereas most somatostatinergic hilar neurons were negative for MOR and DOR mRNA, somatostatinergic oriens layer neurons frequently expressed these receptors. Taken together, weak expression of MOR and DOR genes in hippocampal principal cells is in concordance with direct opioid-mediated inhibition of principal cells. However, strong expression of the MOR and DOR genes in the hippocampus is restricted to gamma-aminobutyric acid (GABA)ergic neurons, with DORs being selectively expressed in the parvalbumin- and somatostatin-containing subpopulations. Activation of MOR and/or DOR in parvalbumin- and somatostatin-containing neurons, which provide GABAergic inhibition to the perisomatic and distal dendritic regions of principal cells, respectively, is likely to facilitate principal cell excitation.