Rationale: Hippocampal interneurons release γ-aminobutyric acid (GABA) and produce fast GABAA- and slow GABAB-inhibitory postsynaptic potentials (IPSPs). The regulation of GABAB eIPSPs or the interneurons that produce them are not well understood. In addition, while both μ-opioid receptors (μORs) and cannabinoid CB1R receptors (CB1Rs) are present on hippocampal interneurons, it is not clear how these two systems interact. Objectives: This study tests the hypotheses that: (1) all interneurons can initiate both GABAA and GABAB inhibitory postsynaptic potentials; (2) GABAB responses are insensitive to mGluR-triggered, endocannabinoid (eCB)-mediated inhibitory long-term depression (iLTD); (3) GABAB responses are produced by interneurons that express μOR; and (4) CB1R-dependent and μOR-dependent response interact. Materials and methods: Pharmacological and electrophysiological approaches were used in acute rat hippocampal slices. High resistance microelectrode recordings were made from pyramidal cells, while interneurons were stimulated extracellularly. Results: GABAB responses were found to be produced by interneurons that release GABA via either presynaptic N-type or P/Q-type calcium channels but that they are insensitive to suppression by eCBs or eCB-mediated iLTD. GABA B IPSPs were sensitive to suppression by a μOR agonist, suggesting a major source of GABAB responses is the μOR-expressing interneuron population. A small eCB-iLTD (10% eIPSP reduction) persisted in conotoxin. eCB-iLTD was blocked by a μOR agonist in 6/13 slices. Conclusions: GABAB responses cannot be produced by all interneurons. CB1R or μOR agonists will differentially alter the balance of activity in hippocampal circuits. CB1R- and μOR-mediated responses can interact.
Bibliographical noteFunding Information:
Acknowledgements This work was supported by NIH R01 MH077277 and RO1 DA 014625 to B.E.A. We thank Dr. M. A. Karson for her comments on a draft of this manuscript and for help in preparing the reference list. We also thank K. Gormley at the NIDA for providing the SR141716A.
- Paired-pulse ratio