Abstract：
:Neuregulin-1 (NRG1) gene variants are associated with increased genetic risk for schizophrenia. It is unclear whether risk haplotypes cause elevated or decreased expression of NRG1 in the brains of schizophrenia patients, given that both findings have been reported from autopsy studies. To study NRG1 functions in vivo, we generated mouse mutants with reduced and elevated NRG1 levels and analyzed the impact on cortical functions. Loss of NRG1 from cortical projection neurons resulted in increased inhibitory neurotransmission, reduced synaptic plasticity, and hypoactivity. Neuronal overexpression of cysteine-rich domain (CRD)-NRG1, the major brain isoform, caused unbalanced excitatory-inhibitory neurotransmission, reduced synaptic plasticity, abnormal spine growth, altered steady-state levels of synaptic plasticity-related proteins, and impaired sensorimotor gating. We conclude that an "optimal" level of NRG1 signaling balances excitatory and inhibitory neurotransmission in the cortex. Our data provide a potential pathomechanism for impaired synaptic plasticity and suggest that human NRG1 risk haplotypes exert a gain-of-function effect.
journal_name
Cell Repjournal_title
Cell reportsauthors
Agarwal A,Zhang M,Trembak-Duff I,Unterbarnscheidt T,Radyushkin K,Dibaj P,Martins de Souza D,Boretius S,Brzózka MM,Steffens H,Berning S,Teng Z,Gummert MN,Tantra M,Guest PC,Willig KI,Frahm J,Hell SW,Bahn S,Rossner MJdoi
10.1016/j.celrep.2014.07.026subject
Has Abstractpub_date
2014-08-21 00:00:00pages
1130-45issue
4issn
2211-1247pii
S2211-1247(14)00610-Xjournal_volume
8pub_type
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