Distinctions among GABAA and GABAB responses revealed by calcium channel antagonists, cannabinoids, opioids, and synaptic plasticity in rat hippocampus.
BACKGROUND
Hippocampal interneurons release gamma-aminobutyric acid (GABA) and produce fast GABA(A)- and slow GABA(B)-inhibitory postsynaptic potentials (IPSPs). The regulation of GABA(B) eIPSPs or the interneurons that produce them are not well understood. In addition, while both micro-opioid receptors (microORs) and cannabinoid CB1R receptors (CB1Rs) are present on hippocampal interneurons, it is not clear how these two systems interact.


OBJECTIVE
This study tests the hypotheses that: (1) all interneurons can initiate both GABA(A) and GABA(B) inhibitory postsynaptic potentials; (2) GABA(B) responses are insensitive to mGluR-triggered, endocannabinoid (eCB)-mediated inhibitory long-term depression (iLTD); (3) GABA(B) responses are produced by interneurons that express microOR; and (4) CB1R-dependent and microOR-dependent response interact.


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
GABA(B) 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 microOR agonist, suggesting a major source of GABA(B) responses is the microOR-expressing interneuron population. A small eCB-iLTD (10% eIPSP reduction) persisted in conotoxin. eCB-iLTD was blocked by a microOR agonist in 6/13 slices.


CONCLUSIONS
GABA(B) responses cannot be produced by all interneurons. CB1R or microOR agonists will differentially alter the balance of activity in hippocampal circuits. CB1R- and microOR-mediated responses can interact.
Lafourcade
Carlos A
CA
Departments of Physiology and Psychiatry, University of Maryland School of Medicine, 655 West Baltimore Street, BRB 5-025, Baltimore, MD 21201, USA.
Alger
Bradley E
BE
D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002186:Cannabinoids / Q000494:pharmacology*; D020916:Conotoxins / Q000494:pharmacology; D004594:Electrophysiology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects*; D007395:Interneurons / Q000187:drug effects; D008297:Male; D009473:Neuronal Plasticity / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D043884:Receptor, Cannabinoid, CB1 / Q000187:drug effects; D011963:Receptors, GABA-A / Q000187:drug effects*; D018080:Receptors, GABA-B / Q000187:drug effects*; D017450:Receptors, Opioid, mu / Q000187:drug effects; D013569:Synapses / Q000187:drug effects*
D000701:Analgesics, Opioid; D002121:Calcium Channel Blockers; D002186:Cannabinoids; D020916:Conotoxins; D043884:Receptor, Cannabinoid, CB1; D011963:Receptors, GABA-A; D018080:Receptors, GABA-B; D017450:Receptors, Opioid, mu