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

Sam A. Booker, Daniel Althof, Anna Gross, Desiree Loreth, Johanna Müller, Andreas Unger, Bernd Fakler, A. Varró, Masahiko Watanabe, Martin Gassmann, Bernhard Bettler, Ryuichi Shigemoto, Imre Vida, Ákos Kulik

Research output: Contribution to journalArticle

9 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)2318-2334
Number of pages17
JournalCerebral cortex (New York, N.Y. : 1991)
Volume27
Issue number3
DOIs
Publication statusPublished - Mar 1 2017

    Fingerprint

Keywords

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

ASJC Scopus subject areas

  • Cognitive Neuroscience
  • Cellular and Molecular Neuroscience

Cite this

Booker, S. A., Althof, D., Gross, A., Loreth, D., Müller, J., Unger, A., Fakler, B., Varró, A., Watanabe, M., Gassmann, M., Bettler, B., Shigemoto, R., Vida, I., & Kulik, Á. (2017). KCTD12 Auxiliary Proteins Modulate Kinetics of GABAB Receptor-Mediated Inhibition in Cholecystokinin-Containing Interneurons. Cerebral cortex (New York, N.Y. : 1991), 27(3), 2318-2334. https://doi.org/10.1093/cercor/bhw090