Fig. 1

Summary of schizophrenia-related phenotypes in various GluN1 mutant mice. GluN1 knockdown regardless of cell-types ("hypomorph mouse") presents several aspects of schizophrenia-related signs. GluN1 deletionin glutamatergic neurons (Emx1-cre KO and Nex-cre KO)during development both result in the phenotypes too severe to consider as schizophrenia-related signs. GluN1 deletion in forebrain principal neurons in adulthood (G35-3 cre-KO and αCaMKII cre-KO) appears to be sufficient to cause some neuropsychiatric signs, including E/I balance increase and cognitive dysfunction; however, insufficient to induce abnormalities of local GABA neurons seen in schizophrenia pathophysiology. Mouse strains with black arrows (top two strains) received genetic manipulation targeted to all the cells throughout the development. The manipulation in the mouse with blue arrows (bottom three strains) was largely restricted to the particular cell-types of forebrain principal neurons. Thick arrows in the left panel show the period of knockout occurring in the designated KO cell-type in the cortex. Hyphen denotes no data in the right Table. ROS reactive oxygen species. PPI, prepulse inhibition of startle reflex