Ivy and neurogliaform interneurons are a major target of μ-opioid receptor modulation.
μ-Opioid receptors (μORs) are selectively expressed on interneurons in area CA1 of the hippocampus. Fast-spiking, parvalbumin-expressing, basket cells express μORs, but circumstantial evidence suggests that another major, unidentified, GABAergic cell class must also be modulated by μORs. Here we report that the abundant, dendritically targeting, neurogliaform family of cells (Ivy and neurogliaform cells) is a previously unrecognized target of direct modulation by μORs. Ivy and neurogliaform cells are not only numerous but also have unique properties, including promiscuous gap junctions formed with various interneuronal subtypes, volume transmission, and the ability to produce a postsynaptic GABA(B) response after a single presynaptic spike. Using a mouse line expressing green fluorescent protein under the neuropeptide Y promoter, we find that, across all layers of CA1, activation of μORs hyperpolarizes Ivy and neurogliaform cells. Furthermore, paired recordings between synaptically coupled Ivy and pyramidal cells show that Ivy cell terminals are dramatically inhibited by μOR activation. Effects in Ivy and neurogliaform cells are seen at similar concentrations of agonist as those producing inhibition in fast-spiking parvalbumin basket cells. We also report that Ivy cells display the recently described phenomenon of persistent firing, a state of continued firing in the absence of continued input, and that induction of persistent firing is inhibited by μOR activation. Together, these findings identify a major, previously unrecognized, target of μOR modulation. Given the prominence of this cell type in and beyond CA1, as well as its unique role in microcircuitry, opioid modulation of neurogliaform cells has wide implications.
Department of Anatomy and Neurobiology, University of California, Irvine, California 92697-1280, USA. ekrookma@uci.edu
Esther
E
Krook-Magnuson
Lillian
L
Luu
Sang-Hun
SH
Lee
Csaba
C
Varga
Ivan
I
Soltesz
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000701:Analgesics, Opioid / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D001703:Biophysics; D015816:Cell Adhesion Molecules, Neuronal / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)- / Q000494:pharmacology; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology; D066298:In Vitro Techniques; D007395:Interneurons / Q000145:classification* / Q000166:cytology / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D009292:Narcotic Antagonists / Q000494:pharmacology; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009478:Neuropeptide Y / Q000235:genetics; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D010320:Parvalbumins / Q000378:metabolism; D018408:Patch-Clamp Techniques / Q000379:methods; D010455:Peptides / Q000494:pharmacology; D037121:Plant Lectins / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D017450:Receptors, Opioid, mu / Q000172:deficiency / Q000378:metabolism*; D000091042:Reelin Protein; D012697:Serine Endopeptidases / Q000378:metabolism; D018709:Statistics, Nonparametric; D055366:Synaptic Potentials / Q000187:drug effects / Q000235:genetics
D000701:Analgesics, Opioid; D015816:Cell Adhesion Molecules, Neuronal; D016326:Extracellular Matrix Proteins; D009292:Narcotic Antagonists; D009419:Nerve Tissue Proteins; D009478:Neuropeptide Y; D010320:Parvalbumins; D010455:Peptides; D037121:Plant Lectins; D017450:Receptors, Opioid, mu; D000091042:Reelin Protein; C034981:tomato lectin; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D049452:Green Fluorescent Proteins; C009862:connective tissue-activating peptide; D052250:Nitric Oxide Synthase Type III; D012697:Serine Endopeptidases