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Cereb Cortex. 2017 Mar 1;27(3):2318-2334. doi: 10.1093/cercor/bhw090.

KCTD12 Auxiliary Proteins Modulate Kinetics of GABAB Receptor-Mediated Inhibition in Cholecystokinin-Containing Interneurons.

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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.
Institute of Physiology.
Department of Physiology, Ruhr University Bochum, Bochum 44801, Germany.
BIOSS Centre for Biological Signalling Studies, University of Freiburg, Freiburg 79104, Germany.
Department of Cellular and Molecular Physiology, Institute of Translational Medicine, University of Liverpool, Liverpool L69 3BX, UK.
Department of Anatomy, Graduate School of Medicine, Hokkaido University, Sapporo 0608638, Japan.
Department of Biomedicine, Pharmazentrum, University of Basel, Basel 4056, Switzerland.
Institute of Science and Technology Austria, Klosterneuburg 3400, Austria.


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.


Kir3 channels; desensitization; disinhibition; immunoelectron microscopy; network activity

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