title: KCTD12 Auxiliary Proteins Modulate Kinetics of GABAB Receptor-Mediated Inhibition in Cholecystokinin-Containing Interneurons.
abstract: Cholecystokinin-expressing interneurons (CCK-INs) mediate behavior state-dependent inhibition in cortical circuits and themselves receive strong GABAergic input. However, it remains unclear to what extent GABAB receptors (GABABRs) contribute to their inhibitory control. Using immunoelectron microscopy, we found that CCK-INs in the rat hippocampus possessed high levels of dendritic GABABRs and KCTD12 auxiliary proteins, whereas postsynaptic effector Kir3 channels were present at lower levels. Consistently, whole-cell recordings revealed slow GABABR-mediated inhibitory postsynaptic currents (IPSCs) in most CCK-INs. In spite of the higher surface density of GABABRs in CCK-INs than in CA1 principal cells, the amplitudes of IPSCs were comparable, suggesting that the expression of Kir3 channels is the limiting factor for the GABABR currents in these INs. Morphological analysis showed that CCK-INs were diverse, comprising perisomatic-targeting basket cells (BCs), as well as dendrite-targeting (DT) interneurons, including a previously undescribed DT type. GABABR-mediated IPSCs in CCK-INs were large in BCs, but small in DT subtypes. In response to prolonged activation, GABABR-mediated currents displayed strong desensitization, which was absent in KCTD12-deficient mice. This study highlights that GABABRs differentially control CCK-IN subtypes, and the kinetics and desensitization of GABABR-mediated currents are modulated by KCTD12 proteins.
authors.affiliation: Institute for Integrative Neuroanatomy and Neurocure Cluster of Excellence, Charité Universitätmedizin Berlin, Berlin 10116, Germany.|Centre for Integrative Physiology, University of Edinburgh, Edinburgh EH8 9XD, UK.
authors.forename: Sam A
authors.initials: SA
authors.lastname: Booker
authors.affiliation: Institute of Physiology.
authors.forename: Daniel
authors.initials: D
authors.lastname: Althof
authors.affiliation: Institute of Physiology.
authors.forename: Anna
authors.initials: A
authors.lastname: Gross
authors.affiliation: Institute of Physiology.
authors.forename: Desiree
authors.initials: D
authors.lastname: Loreth
authors.affiliation: Institute of Physiology.
authors.forename: Johanna
authors.initials: J
authors.lastname: Müller
authors.affiliation: Institute of Physiology.|Department of Physiology, Ruhr University Bochum, Bochum 44801, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Unger
authors.affiliation: Institute of Physiology.|BIOSS Centre for Biological Signalling Studies, University of Freiburg, Freiburg 79104, Germany.
authors.forename: Bernd
authors.initials: B
authors.lastname: Fakler
authors.affiliation: Department of Cellular and Molecular Physiology, Institute of Translational Medicine, University of Liverpool, Liverpool L69 3BX, UK.
authors.forename: Andrea
authors.initials: A
authors.lastname: Varro
authors.affiliation: Department of Anatomy, Graduate School of Medicine, Hokkaido University, Sapporo 0608638, Japan.
authors.forename: Masahiko
authors.initials: M
authors.lastname: Watanabe
authors.affiliation: Department of Biomedicine, Pharmazentrum, University of Basel, Basel 4056, Switzerland.
authors.forename: Martin
authors.initials: M
authors.lastname: Gassmann
authors.affiliation: Department of Biomedicine, Pharmazentrum, University of Basel, Basel 4056, Switzerland.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Bettler
authors.affiliation: Institute of Science and Technology Austria, Klosterneuburg 3400, Austria.
authors.forename: Ryuichi
authors.initials: R
authors.lastname: Shigemoto
authors.affiliation: Institute for Integrative Neuroanatomy and Neurocure Cluster of Excellence, Charité Universitätmedizin Berlin, Berlin 10116, Germany.
authors.forename: Imre
authors.initials: I
authors.lastname: Vida
authors.affiliation: Institute of Physiology.|BIOSS Centre for Biological Signalling Studies, University of Freiburg, Freiburg 79104, Germany.
authors.forename: Ákos
authors.initials: Á
authors.lastname: Kulik
mesh_terms: D000818:Animals; D056547:CA1 Region, Hippocampal / Q000378:metabolism / Q000648:ultrastructure; D002766:Cholecystokinin / Q000378:metabolism*; D003712:Dendrites / Q000378:metabolism / Q000648:ultrastructure; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels / Q000378:metabolism*; D007150:Immunohistochemistry; D053444:Inhibitory Postsynaptic Potentials / Q000502:physiology*; D007395:Interneurons / Q000378:metabolism* / Q000648:ultrastructure; D008297:Male; D016253:Microscopy, Immunoelectron; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000378:metabolism*; D017208:Rats, Wistar; D011963:Receptors, GABA-A / Q000378:metabolism*; D046509:Tissue Culture Techniques
chemical_list: D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels; C546267:Gabrb1 protein, rat; C000617877:KCTD12 protein, rat; D015221:Potassium Channels; D011963:Receptors, GABA-A; D002766:Cholecystokinin
keywords: Kir3 channels; desensitization; disinhibition; immunoelectron microscopy; network activity