title: Extensive overlap of mu-opioid and nicotinic sensitivity in cortical interneurons.
abstract: 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.
authors.affiliation: Laboratoire de Neurobiologie et Diversité Cellulaire, CNRS UMR 7637, Ecole Supérieure de Physique et de Chimie Industrielles, 75005 Paris, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Férézou
authors.forename: Elisa L
authors.initials: EL
authors.lastname: Hill
authors.forename: Bruno
authors.initials: B
authors.lastname: Cauli
authors.forename: Nathalie
authors.initials: N
authors.lastname: Gibelin
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kaneko
authors.forename: Jean
authors.initials: J
authors.lastname: Rossier
authors.forename: Bertrand
authors.initials: B
authors.lastname: Lambolez
mesh_terms: 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
chemical_list: D004745:Enkephalins; D018722:Nicotinic Agonists; D015221:Potassium Channels; D011978:Receptors, Nicotinic; D017450:Receptors, Opioid, mu; D005680:gamma-Aminobutyric Acid