title: Axonal Type III Nrg1 Controls Glutamate Synapse Formation and GluA2 Trafficking in Hippocampal-Accumbens Connections.
abstract: Altered neuregulin 1 (Nrg1)/ErbB signaling and glutamatergic hypofunction have been implicated in the pathophysiology of schizophrenia. Here, we employed gene chimeric ventral hippocampus (vHipp)-nucleus accumbens (nAcc) coculture from mouse, electrophysiology, immunocytochemistry, FM1-43 vesicle fusion, and electron microscopy techniques to examine the pre- and postsynaptic mechanisms of genetic deficits in Nrg1/ErbB signaling-induced glutamatergic dysfunctions. Reduced presynaptic type III Nrg1 expression along vHipp axons decreases the number of glutamate synapses and impairs GluA2 trafficking in the postsynaptic nAcc neurons, resulting in decreased frequency and amplitude of miniature EPSCs (mEPSCs). Reduced expression of axonal type III Nrg1 along vHipp projections also decreases functional synaptic vesicle (SV) clustering and vesicular trafficking to presynaptic vHipp axonal terminals. These findings suggest that Nrg1/ErbB signaling modulate glutamatergic transmission via both pre- and postsynaptic mechanisms.
authors.affiliation: Department of Neurobiology and Behavior, Center for Nervous System Disorder, Stony Brook University , Stony Brook, NY 11794.
authors.forename: Chongbo
authors.initials: C
authors.lastname: Zhong
authors.affiliation: Department of Neurobiology and Behavior, Center for Nervous System Disorder, Stony Brook University , Stony Brook, NY 11794.
authors.forename: Wendy
authors.initials: W
authors.lastname: Akmentin
authors.affiliation: Department of Neuroscience, Tufts University School of Medicine , Boston, MA 02111.
authors.forename: Chuang
authors.identifier: 0000-0001-9580-7381
authors.initials: C
authors.lastname: Du
authors.affiliation: Department of Neurobiology and Behavior, Center for Nervous System Disorder, Stony Brook University , Stony Brook, NY 11794.
authors.forename: Lorna W
authors.identifier: 0000-0001-5851-212X
authors.initials: LW
authors.lastname: Role
authors.affiliation: Department of Pharmacological Science, Center for Nervous System Disorder, Stony Brook University , Stony Brook, NY 11794.
authors.forename: David A
authors.identifier: 0000-0003-4627-3007
authors.initials: DA
authors.lastname: Talmage
mesh_terms: D000818:Animals; D001369:Axons / Q000378:metabolism / Q000648:ultrastructure; D018920:Coculture Techniques; D019706:Excitatory Postsynaptic Potentials; D018698:Glutamic Acid / Q000378:metabolism*; D006624:Hippocampus / Q000378:metabolism* / Q000648:ultrastructure; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D055369:Miniature Postsynaptic Potentials; D020890:Neuregulin-1 / Q000235:genetics / Q000378:metabolism*; D009714:Nucleus Accumbens / Q000378:metabolism* / Q000648:ultrastructure; D018091:Receptors, AMPA / Q000378:metabolism*; D013569:Synapses / Q000378:metabolism* / Q000648:ultrastructure; D046509:Tissue Culture Techniques
chemical_list: D020890:Neuregulin-1; C490581:Nrg1 protein, mouse; D018091:Receptors, AMPA; D018698:Glutamic Acid; C104722:glutamate receptor ionotropic, AMPA 2
keywords: electron microscopy; glutamatergic transmission; neuregulin 1; neurotransmitter release; presynaptic maturation; synaptic vesicle fusion