Extensive overlap of mu-opioid and nicotinic sensitivity in cortical interneurons.
We studied mu-opioid transmission in acute slices of rat neocortex using whole-cell recordings and single-cell reverse transcription-polymerase chain reaction. The mu-opioid receptor (MOR) was found in gamma-aminobutyric acidergic (GABAergic) interneurons that were either layer I cells frequently expressing neuropeptide Y or layers II-V cells expressing vasoactive intestinal peptide and enkephalin (Enk). We found that mu-opioid agonists inhibit these interneurons that are selectively excited by nicotinic agonists. The extensive overlap of mu-opioid and nicotinic responsiveness allowed mu-opioid agonists to inhibit nicotinic excitation of responsive interneurons and of their GABAergic output onto pyramidal cells. Finally, nicotinic stimulation resulted in a dynamic sequence where GABAergic transmission was first enhanced and then depressed below its baseline. This latter disinhibitory effect was prevented by a mu-opioid antagonist, indicating that excitation of nicotinic-responsive interneurons induced the release of endogenous Enk, which in turn led to MOR activation. Our results suggest that neocortical mu-opioid transmission acts as an inhibitory feedback onto nicotinic-responsive interneurons, which may change network excitability and inhibition patterns during cholinergic excitation.
Férézou
Isabelle
I
Laboratoire de Neurobiologie et Diversité Cellulaire, CNRS UMR 7637, Ecole Supérieure de Physique et de Chimie Industrielles, 75005 Paris, France.
Hill
Elisa L
EL
Cauli
Bruno
B
Gibelin
Nathalie
N
Kaneko
Takeshi
T
Rossier
Jean
J
Lambolez
Bertrand
B
D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects / Q000502:physiology*; D004594:Electrophysiology; D004745:Enkephalins / Q000096:biosynthesis / Q000235:genetics; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D007395:Interneurons / Q000187:drug effects / Q000502:physiology*; D019579:Neocortex / Q000187:drug effects / Q000502:physiology; D009415:Nerve Net / Q000166:cytology / Q000502:physiology; D018722:Nicotinic Agonists / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011978:Receptors, Nicotinic / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D017450:Receptors, Opioid, mu / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D009435:Synaptic Transmission / Q000235:genetics / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000502:physiology
D004745:Enkephalins; D018722:Nicotinic Agonists; D015221:Potassium Channels; D011978:Receptors, Nicotinic; D017450:Receptors, Opioid, mu; D005680:gamma-Aminobutyric Acid