Multiple risk pathways for schizophrenia converge in serine racemase knockout mice, a mouse model of NMDA receptor hypofunction

We sought to determine whether the diverse hippocampal neuropathology observed in schizophrenia could be recapitulated in an animal model of NMDA receptor (NMDAR) hypofunction. Serine racemase-deficient (SR^-/-) mice, which lack one of the NMDAR coagonists D-serine, display impaired hippocampal plasticity, as well as the morphological, neurochemical, and cognitive abnormalities consistent with what is observed in schizophrenia. Importantly, treatment in adulthood with D-serine reversed the electrophysiological, neurochemical, and cognitive deficits. These results demonstrate that NMDAR hypofunction can reproduce the hippocampal deficits associated with schizophrenia and point to potential interventions for the currently untreatable negative and cognitive symptoms of this disorder.