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Neuregulin 1 (NRG1) is a large family of EGF domain-containing trophic factors that are widely expressed in the brain.It acts by stimulating ErbB receptor tyrosine kinases including ErbB4.NRG1 signaling has been implicated in various steps of neural development including neuron migration, neurite outgrowth, synapse formation, and myelination.Both NRG 1 and ErbB4 are susceptibility genes of schizophrenia and their expression and activity appear abnormal in the brain of schizophrenic patients although involved pathologic mechanisms are poorly understood.In light of high expression of ErbB4 in parvalbumin (PV)-immunoreactive intemeruons, we have studied its role in synapse formation and synaptic plasticity of PV-positive interneurons by using a combination of in vitro and in vivo techniques.Ⅰ will report and discuss recent data that support the following working models.First, during development, NRG1 appears to promote the formation of excitatory synapses in PV-positive interneuons, probably by stabilizing PSD-95.This effect requires the tyrosine kinase activity of ErbB4.Second, both NRG1 and ErbB4 are expressed in adult brains.NRG 1 was able to stimulate GABA release from PV-positive interneurons and thus reduces the firing of pyramidal neurons.Evidence suggests that acute suppression of the induction of long-term potentiationby NRG1 requires ErbB4 in PV-positive interneurons.Finally, mutant mice where the ErbB4 gene is specifically ablated in PV-positive neurons exhibit schizophrenia-related phenotypes including hyperactivity, reduced prepulse inhibition and impaired working memory.These results highlight a role of NRG1/ErbB4 signaling in PV-positive interneurons in forming GABAergic circuitry and regulating its function and suggest that PV-positive interneurons may be a cellular target of NRG1 signaling in complex behaviors relevant to schizophrenia.These findings contribute to a better understanding of how abnormal NRG 1/ErbB4 signaling may contribute to schizophrenia pathogenesis.