GABAB receptor auxiliary subunits modulate Cav2.3-mediated release from medial habenula terminals
- Institute of Science and Technology Austria, Austria
- University of Basel, Switzerland
- University of Freiburg, Germany
Abstract
The synaptic connection from medial habenula (MHb) to interpeduncular nucleus (IPN) is critical for emotion-related behaviors, and uniquely expresses R-type Ca2+ channels (Cav2.3) and auxiliary GABAB receptor (GBR) subunits, the K+-channel tetramerization domain-containing proteins (KCTDs). Activation of GBRs facilitates or inhibits transmitter release from MHb terminals depending on the IPN subnucleus, but the role of KCTDs is unknown. We therefore examined the localization and function of Cav2.3, GBRs, and KCTDs in this pathway in mice. We show in heterologous cells that KCTD8 and KCTD12b directly bind to Cav2.3 and that KCTD8 potentiates Cav2.3 currents in the absence of GBRs. In the rostral IPN, KCTD8, KCTD12b and Cav2.3 co-localize at the presynaptic active zone. Genetic deletion indicated a bidirectional modulation of Cav2.3-mediated release by these KCTDs with a compensatory increase of KCTD8 in the active zone in KCTD12b-deficient mice. The interaction of Cav2.3 with KCTDs therefore scales synaptic strength independent of GBR activation.
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Article and author information
Author details
Diego Fernández-Fernández
Peter Koppensteiner
Funding
H2020 European Research Council (694539)
- Ryuichi Shigemoto
H2020 European Research Council (692692)
- Peter Jonas
Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (31003A‐172881)
- Bernhard Bettler
H2020 Marie Skłodowska-Curie Actions (665385)
- Cihan Önal
Deutsche Forschungsgemeinschaft (For2143)
- Akos Kulik
Deutsche Forschungsgemeinschaft (BIOSS-2)
- Akos Kulik
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: All experiments were performed in accordance with the license approved by the Austrian Federal Ministry of Science and Research (Animal license number: BMWFW-66.018/0012-WF/V/3b/2016) and the Austrian and EU animal laws.
Copyright
© 2021, Bhandari et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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GABAB receptor auxiliary subunits modulate Cav2.3-mediated release from medial habenula terminals
eLife 10:e68274.
https://doi.org/10.7554/eLife.68274
