Distinctions among GABAA and GABAB responses revealed by calcium channel antagonists, cannabinoids, opioids, and synaptic plasticity in rat hippocampus

Carlos A. Lafourcade, Bradley E. Alger

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

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.
Original languageAmerican English
Pages (from-to)539-549
Number of pages11
JournalPsychopharmacology
Volume198
Issue number4
DOIs
StatePublished - 1 Jul 2008
Externally publishedYes

Keywords

  • Agatoxin
  • CA1
  • CB1R
  • Conotoxin
  • DAMGO
  • Endocannabinoid
  • iLTD
  • mGluR
  • Paired-pulse ratio
  • SR141716A

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