Adult brain function and behavior are influenced by neuronal network formation during development. Genetic susceptibility factors for adult psychiatric illnesses, such as Neuregulin-1 and Disrupted-in-Schizophrenia-1 (DISC1), influence adult high brain functions, including cognition and information processing. These factors have roles during neurodevelopment and are likely to cooperate, forming pathways or "signalosomes." Here we report the potential to generate an animal model via in utero gene transfer in order to address an important question of how nonlethal deficits in early development may affect postnatal brain maturation and high brain functions in adulthood, which are impaired in various psychiatric illnesses such as schizophrenia. We show that transient knockdown of DISC1 in the pre- and perinatal stages, specifically in a lineage of pyramidal neurons mainly in the prefrontal cortex, leads to selective abnormalities in postnatal mesocortical dopaminergic maturation and behavioral abnormalities associated with disturbed cortical neurocircuitry after puberty.
Niwa, MinaeKamiya, AtsushiMurai, RinaKubo, Ken-ichiroGruber, Aaron JTomita, KenjiLu, LinglingTomisato, ShutaJaaro-Peled, HannaSeshadri, SauravHiyama, HidekiHuang, BeverlyKohda, KazuhisaNoda, YukihiroO'Donnell, PatricioNakajima, KazunoriSawa, AkiraNabeshima, ToshitakaMH-069853/MH/NIMH NIH HHS/United StatesMH-084018/MH/NIMH NIH HHS/United StatesMH-088753/MH/NIMH NIH HHS/United StatesP20 MH084018-04/MH/NIMH NIH HHS/United StatesR01 MH069853-08/MH/NIMH NIH HHS/United StatesRC1 MH088753-02/MH/NIMH NIH HHS/United StatesResearch Support, N.I.H., ExtramuralResearch Support, Non-U.S. Gov'tUnited StatesNeuronNeuron. 2010 Feb 25;65(4):480-9. doi: 10.1016/j.neuron.2010.01.019.