Neuregulin 3 promotes excitatory synapse formation on hippocampal interneurons |
| |
| Authors: | Thomas Müller Stephanie Braud René Jüttner Birgit C Voigt Katharina Paulick Maria E Sheean Constantin Klisch Dilansu Gueneykaya Fritz G Rathjen Jörg RP Geiger James FA Poulet Carmen Birchmeier |
| |
| Affiliation: | 1. Developmental Biology/Signal Transduction Group, Max‐Delbrueck‐Centrum in the Helmholtz Association, Berlin, Germany;2. Institute of Neurophysiology, Charité – Universit?tsmedizin Berlin, Berlin, Germany;3. Developmental Neurobiology Group, Max‐Delbrueck‐Centrum in the Helmholtz Association, Berlin, Germany;4. Neural Circuits and Behaviour Group, Max‐Delbrueck‐Centrum in the Helmholtz Association, Berlin, Germany;5. Cellular Neuroscience Group, Max‐Delbrueck‐Centrum in the Helmholtz Association, Berlin, Germany;6. Neuroscience Research Center and Cluster of Excellence NeuroCure, Charité‐Universit?tsmedizin Berlin, Berlin, Germany |
| |
| Abstract: | Hippocampal GABAergic interneurons are crucial for cortical network function and have been implicated in psychiatric disorders. We show here that Neuregulin 3 (Nrg3), a relatively little investigated low‐affinity ligand, is a functionally dominant interaction partner of ErbB4 in parvalbumin‐positive (PV) interneurons. Nrg3 and ErbB4 are located pre‐ and postsynaptically, respectively, in excitatory synapses on PV interneurons in vivo. Additionally, we show that ablation of Nrg3 results in a similar phenotype as the one described for ErbB4 ablation, including reduced excitatory synapse numbers on PV interneurons, altered short‐term plasticity, and disinhibition of the hippocampal network. In culture, presynaptic Nrg3 increases excitatory synapse numbers on ErbB4+ interneurons and affects short‐term plasticity. Nrg3 mutant neurons are poor donors of presynaptic terminals in the presence of competing neurons that produce recombinant Nrg3, and this bias requires postsynaptic ErbB4 but not ErbB4 kinase activity. Furthermore, when presented by non‐neuronal cells, Nrg3 induces postsynaptic membrane specialization. Our data indicate that Nrg3 provides adhesive cues that facilitate excitatory neurons to synapse onto ErbB4+ interneurons. |
| |
| Keywords: | ErbB4 GABAergic interneurons hippocampus synaptogenesis |
|
|
