Parvalbumin interneurons in the nucleus accumbens regulate impairment of risk avoidance inDISC1transgenic mice

One 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, whether DISC1 mice models have an impairment in avoiding potential risks is still not fully understood. In the present study, we used DISC1-N terminal truncation ( DISC1-N TM ) mice to study cognitive abilities related to potential risks. We found that DISC1-N TM mice 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 in DISC1-N TM mice. Meanwhile, in vivo electrophysiological recordings showed that firing rates of fast spiking neurons (FS) in the NAc significantly decreased in DISC1-N TM mice 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 truncated DISC1 gene. Furthermore, we found through in vitro patch clamp recording that the frequency of action potentials stimulated by current injection was lower in parvalbumin (PV) neurons in the NAc of DISC1-N TM mice than their wild-type littermates. Risk-avoidance impairments in DISC1-N TM mice were rescued using optogenetic tools that activated NAc PV neurons. Finally, we inhibited activitiy of NAc PV neurons in PV-Cre mice, which mimicked the risk-avoidance impairment found in the DISC1-N TM mice during tests on the elevated zero maze. Taken together, our findings confirmed a cognitive impairment in DISC1-N TM mice related to risk recognition and suggests that reduced excitability of NAc PV neurons may be responsible.