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Neuregulin (NRG) and its cognate neuronal receptor tyrosine kinase ErbB4 are genetically associated with increased risk for schizophrenia and its endophenotyes. 1–4 Moreover, diseaseassociated intronic and splice variants for ErbB4, 5 and altered NRG1, NRG3 and ErbB4 levels 6–8 in the brains of schizophrenic patients have been reported. Remarkably, mice with mutations in nrg1, nrg2, nrg3 and erbb4 display numerous behavioral abnormalities resembling psychiatric symptoms in affected individuals. 9–16 Experiments in rodents suggest that NRG/ErbB4 signaling modulates several neurotransmitter systems including GABA, glutamate, acetylcholine and dopamine (DA; see refs 3, 17).

As ErbB4 is highly expressed in GABAergic parvalbumin-positive (PV+) basket cells but absent from glutamatergic neurons, 18–20 and this interneuron subtype is selectively affected in the dorsal prefrontal cortex (DLPFC) of …