AbstractOne strong survival instinct in animals is to approach things that are of benefit and avoid risk. In humans, a large portion of mental disorders are accompanied by cognition-related impairments including the inability to recognize potential risks. One of the most important genes involved in risk behavior is disrupted-in-schizophrenia-1 (DISC1), and animal models where this gene has some dysfunction show cognitive impairments. However, whetherDISC1mice models have an impairment in avoiding potential risks is still not fully understood. In the present study, we used DISC1-N terminal truncation (DISC1-NTM) mice to study cognitive abilities related to potential risks. We found thatDISC1-NTMmice were impaired in risk avoidance on the elevated plus maze (EPM) test, and showed impairment in social preference in a three-chamber social interaction test. Staining for c-Fos following the EPM indicated that the nucleus accumbens (NAc) was associated with risk avoidance behavior inDISC1-NTMmice. Meanwhile,in vivoelectrophysiological recordings showed that firing rates of fast spiking neurons (FS) in the NAc significantly decreased inDISC1-NTMmice following tamoxifen administration. In addition, theta band power was lower when mice shuttled from the safe (closed) arms to the risky (open) arms, an effect which disappeared after induction of the truncatedDISC1gene. Furthermore, we found throughin vitropatch clamp recording that the frequency of action potentials stimulated by current injection was lower in parvalbumin (PV) neurons in the NAc ofDISC1-NTMmice than their wild-type littermates. Risk-avoidance impairments inDISC1-NTMmice were rescued using optogenetic tools that activated NAcPVneurons. Finally, we inhibited activitiy of NAcPVneurons in PV-Cre mice, which mimicked the risk-avoidance impairment found in theDISC1-NTMmice during tests on the elevated zero maze. Taken together, our findings confirmed a cognitive impairment inDISC1-NTMmice related to risk recognition and suggests that reduced excitability of NAcPVneurons may be responsible.