RT Journal Article SR Electronic T1 Axonal Type III Nrg1 Controls Glutamate Synapse Formation and GluA2 Trafficking in Hippocampal-Accumbens Connections JF eneuro JO eNeuro FD Society for Neuroscience SP ENEURO.0232-16.2017 DO 10.1523/ENEURO.0232-16.2017 VO 4 IS 1 A1 Chongbo Zhong A1 Wendy Akmentin A1 Chuang Du A1 Lorna W. Role A1 David A. Talmage YR 2017 UL http://www.eneuro.org/content/4/1/ENEURO.0232-16.2017.abstract AB 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.