Neuregulin 3 promotes excitatory synapse formation on hippocampal interneurons

• Thomas Müller ^[1] ; Stephanie Braud ^[2] ; René Jüttner ^[3] ; Birgit C Voigt ^[4] ; Katharina Paulick ^[1] ; Maria E Sheean ^[1] ; Constantin Klisch ^[2] ; Dilansu Gueneykaya ^[5] ; Fritz G Rathjen ^[3] ; Jörg RP Geiger ^[2] ; James FA Poulet ^[6] ; Carmen Birchmeier ^[1]
  1. [1] 1 Developmental Biology/Signal Transduction Group Max‐Delbrueck‐Centrum in the Helmholtz Association Berlin Germany
  2. [2] 2 Institute of Neurophysiology Charité – Universitätsmedizin Berlin Berlin Germany
  3. [3] 3 Developmental Neurobiology Group Max‐Delbrueck‐Centrum in the Helmholtz Association Berlin Germany
  4. [4] 4 Neural Circuits and Behaviour Group Max‐Delbrueck‐Centrum in the Helmholtz Association Berlin Germany
  5. [5] 5 Cellular Neuroscience Group Max‐Delbrueck‐Centrum in the Helmholtz Association Berlin Germany
  6. [6] 4 Neural Circuits and Behaviour Group Max‐Delbrueck‐Centrum in the Helmholtz Association Berlin Germany; 6 Neuroscience Research Center and Cluster of Excellence NeuroCure Charité‐Universitätsmedizin Berlin Berlin Germany

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• Localización: EMBO journal: European Molecular Biology Organization, ISSN 0261-4189, Vol. 37, Nº. 17, 2018
• Idioma: inglés
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  • 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.