Schizophrenia is one of the most severe mental illnesses affecting about 1% of the whole population in the world.Extensive studies have been done for this mental disorder in the past one hundred years since Dr.Bleuler coined the term "schizophrenia" in 1911.A number of hypotheses have been proposed to understand this most complicated brain disorder.This presentation will be starting from a very brief introduction of those main hypotheses in schizophrenia research, and will be focusing on a new hypothesis of schizophrenia, the oligodendrocyte hypothesis.It will be summarizing the main supporting evidence for this new hypothesis under the categories of white matter changes in schizophrenic brains in post-mortem and MRI studies, alterations in genes controlling the structure and function of oligodendrocytes in patients with schizophrenia, schizophrenia symptoms seen in patients with white matter diseases such as multiple sclerosis, and effects of anti-psychotics on oligodendrocytes and myelination.In the following introduction of animal models examining a putative role of altered oligodendrocytes in the pathophysiology of schizophrenia, the presentation will be emphasizing a new animal model developed by the team of the author, who found that C57BL/6 mice fed with cuprizone-containing (0.2%) diet show certain behavioral changes relevant to the positive, negative, and cognitive symptoms seen in patients with schizophrenia.More relevantly, these cuprizoneinduced changes differently respond to haloperidol and some new anti-psychotics tested.In previous studies, cuprizonefeeding was shown to cause demyelination and myelin break-down in specific brain structures of C57BL/6 mice thus used as an animal model of multiple sclerosis.Our results suggest that the cuprizone-fed mice may be used as a platform for the exploration of roles of altered oligodendrocytes and white matter in the pathogenesis and treatment of schizophrenia.