Postsynaptic GABABRs Inhibit L-Type Calcium Channels and Abolish Long-Term Potentiation in Hippocampal Somatostatin Interneurons
Sam A. Booker,
Desiree Loreth,
Annabelle L. Gee,
Masahiko Watanabe,
Peter C. Kind,
David J.A. Wyllie,
Ákos Kulik,
Imre Vida
Affiliations
Sam A. Booker
Institute for Integrative Neuroanatomy, NeuroCure Cluster of Excellence, Charité - Universitätmedizin Berlin, 10117 Berlin, Germany; Centre for Discovery Brain Sciences, University of Edinburgh, Edinburgh, UK; Simons Initiative for the Developing Brain, University of Edinburgh, Edinburgh, UK; Patrick Wild Centre for Autism Research, University of Edinburgh, Edinburgh, UK; Institute for Neuroscience, Glasgow University, Glasgow G12 8QQ, UK
Desiree Loreth
Institute of Physiology, Faculty of Medicine, University of Freiburg, Hermann-Herder-Str. 7, 79104 Freiburg, Germany
Annabelle L. Gee
Institute for Neuroscience, Glasgow University, Glasgow G12 8QQ, UK
Masahiko Watanabe
Department of Anatomy, Graduate School of Medicine, Hokkaido University, Sapporo 0608638, Japan
Peter C. Kind
Centre for Discovery Brain Sciences, University of Edinburgh, Edinburgh, UK; Simons Initiative for the Developing Brain, University of Edinburgh, Edinburgh, UK; Patrick Wild Centre for Autism Research, University of Edinburgh, Edinburgh, UK
David J.A. Wyllie
Centre for Discovery Brain Sciences, University of Edinburgh, Edinburgh, UK; Simons Initiative for the Developing Brain, University of Edinburgh, Edinburgh, UK; Patrick Wild Centre for Autism Research, University of Edinburgh, Edinburgh, UK
Ákos Kulik
Institute of Physiology, Faculty of Medicine, University of Freiburg, Hermann-Herder-Str. 7, 79104 Freiburg, Germany; Centre for Biological Signalling Studies (BIOSS), University of Freiburg, Schänzle-Str. 18, 79104 Freiburg, Germany; Corresponding author
Imre Vida
Institute for Integrative Neuroanatomy, NeuroCure Cluster of Excellence, Charité - Universitätmedizin Berlin, 10117 Berlin, Germany; Institute for Neuroscience, Glasgow University, Glasgow G12 8QQ, UK; Corresponding author
Summary: Inhibition provided by local GABAergic interneurons (INs) activates ionotropic GABAA and metabotropic GABAB receptors (GABABRs). Despite GABABRs representing a major source of inhibition, little is known of their function in distinct IN subtypes. Here, we show that, while the archetypal dendritic-inhibitory somatostatin-expressing INs (SOM-INs) possess high levels of GABABR on their somato-dendritic surface, they fail to produce significant postsynaptic inhibitory currents. Instead, GABABRs selectively inhibit dendritic CaV1.2 (L-type) Ca2+ channels on SOM-IN dendrites, leading to reduced calcium influx and loss of long-term potentiation at excitatory input synapses onto these INs. These data provide a mechanism by which GABABRs can contribute to disinhibition and control the efficacy of extrinsic inputs to hippocampal networks. : Booker et al. show that GABAB receptors are highly expressed on somatostatin interneuron dendrites. Rather than activating Kir3 channels, they preferentially co-cluster with, and negatively couple to, L-type calcium channels inhibiting long-term potentiation at excitatory inputs. Keywords: GABAergic interneurons, feedback inhibition, GABAB receptors, dendrites, Cav1.2 channels, synaptic plasticity, hippocampus, electron microscopy, whole-cell recording, multi-photon imaging
