Reduced Firing of Nucleus Accumbens Parvalbumin Interneurons Impairs Risk Avoidance in DISC1 Transgenic Mice

AbstractA strong animal survival instinct is to approach objects and situations that are of benefit and to avoid risk. In humans, a  large proportion of mental disorders are accompanied by impairments in risk avoidance. One of the most important genes involved in mental disorders is disrupted-in-schizophrenia-1 (DISC1), and animal models in which this gene has some level of dysfunction show emotion-related impairments. However, it is not known whetherDISC1 mouse models have an impairment in avoiding potential risks. In the present study, we usedDISC1-N terminal truncation (DISC1-NTM) mice to investigate risk avoidance and found that these mice were impaired in risk avoidance on the elevated plus maze (EPM) and showed reduced social preference in a three-chamber social interaction test. Following EPM tests, c-Fos expression levels indicated that the nucleus accumbens (NAc) was associated with risk-avoidance behavior inDISC1-NTM mice. In addition,in vivo electrophysiological recordings following tamoxifen administration showed that the firing rates of fast-spiking neurons (FS) in the NAc were significantly lower inDISC1-NTM mice than in wild-type (WT) mice. In addition,in vitro patch clamp recording revealed that the frequency of action potentials stimulated by current injection was lower in parvalbumin (PV) neurons in the NAc ofDISC1-NTM mice than in WT controls. The impairment of risk avoidance inDISC1-NTM mice was rescued using optogenetic tools that activated NAcPV neuro...
Source: Neuroscience Bulletin - Category: Neuroscience Source Type: research