KCTD12 auxiliary proteins modulate kinetics of GABAB receptor-mediated inhibition in cholecystokinin-containing interneurons
Booker SA, Althof D, Gross A, Loreth D, Müller J, Unger A, Fakler B, Varro A, Watanabe M, Gassmann M, Bettler B, Shigemoto R, Vida I, Kulik Á.
Cholecystokinin-expressing interneurons (CCK-INs) mediate behavior state-dependent inhibition in cortical circuits and themselves receive strong GABAergic input. It remains unclear to what extent 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 Kir3 channels were present at lower levels. Whole-cell recordings revealed slow GABABR-mediated IPSCs in CCK-INs. In spite of the higher surface density of GABABRs in CCK-INs than in principal cells, the amplitudes of IPSCs were comparable, suggesting that the expression of Kir3 is the limiting factor for the GABABR currents in these INs. Morphological analysis showed that CCK-INs were diverse, comprising BCs and DT interneurons, including a previously undescribed DT type. GABABR-mediated IPSCs were large in BCs but small in DT subtypes. In reponse 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.