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Neuregulin 3 promotes excitatory synapse formation on hippocampal interneurons
Author(s) -
Müller Thomas,
Braud Stephanie,
Jüttner René,
Voigt Birgit C,
Paulick Katharina,
Sheean Maria E,
Klisch Constantin,
Gueneykaya Dilansu,
Rathjen Fritz G,
Geiger Jörg RP,
Poulet James FA,
Birchmeier Carmen
Publication year - 2018
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.15252/embj.201798858
Subject(s) - excitatory postsynaptic potential , biology , erbb4 , neuroscience , interneuron , postsynaptic potential , gabaergic , hippocampal formation , inhibitory postsynaptic potential , excitatory synapse , gephyrin , synapse , microbiology and biotechnology , receptor tyrosine kinase , receptor , signal transduction , glycine receptor , biochemistry , glycine , amino acid
Abstract Hippocampal GABA ergic 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.