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KCTD12 Auxiliary Proteins Modulate Kinetics of GABAB Receptor-Mediated Inhibition in Cholecystokinin-Containing Interneurons.
- Source :
-
Cerebral cortex (New York, N.Y. : 1991) [Cereb Cortex] 2017 Mar 01; Vol. 27 (3), pp. 2318-2334. - Publication Year :
- 2017
-
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.<br /> (© The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)
- Subjects :
- Animals
CA1 Region, Hippocampal metabolism
CA1 Region, Hippocampal ultrastructure
Dendrites metabolism
Dendrites ultrastructure
Immunohistochemistry
Interneurons ultrastructure
Male
Microscopy, Immunoelectron
Patch-Clamp Techniques
Rats, Wistar
Tissue Culture Techniques
Cholecystokinin metabolism
G Protein-Coupled Inwardly-Rectifying Potassium Channels metabolism
Inhibitory Postsynaptic Potentials physiology
Interneurons metabolism
Potassium Channels metabolism
Receptors, GABA-A metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1460-2199
- Volume :
- 27
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Cerebral cortex (New York, N.Y. : 1991)
- Publication Type :
- Academic Journal
- Accession number :
- 27073217
- Full Text :
- https://doi.org/10.1093/cercor/bhw090