Hallucinations and delusions are the most prominent symptoms of schizophrenia and characterized by impaired reality testing. Representation-mediated taste aversion (RMTA) has been proposed as a potential behavioral assessment of reality testing and has been applied to a neurodevelopmental rat model of schizophrenia. However, the theory underlying this approach has not been generalized yet with any demonstration of impaired reality testing in other animal models of schizophrenia, such as genetically-modified mice. We devised a RMTA procedure for mice that combines a Pavlovian association protocol pairing odor conditioned stimulus (CS) with sugar reward unconditioned stimulus (US), and a conditioned taste aversion (CTA) method. In this RMTA paradigm, we compared performances of wild-type (PLCβ1+/+) mice and phospholipase C β1 knock-out (PLCβ1-/-) mice which are known as one of the genetic models for schizophrenia. With a minimal amount of initial odor-sugar associative training, both PLCβ1+/+ and PLCβ1-/- mice were able to form an aversion to the sugar reward when the odor CS predicting sugar was paired with nausea. With an extended initial training, however, only PLCβ1-/- mice could form a RMTA. This persistent RMTA displayed by PLCβ1-/- mice shows their inability to distinguish real sugar from the CS-evoked representation of sugar at a stage in associative learning where wild-type mice normally could differentiate the two. These results demonstrate an impaired reality testing first observed in a genetic mouse model of schizophrenia, and suggest that RMTA paradigm may, with general applicability, allow diverse biological approaches to impaired reality testing.

Motherhood goes through preparation, onset and maintenance phases until the natural weaning. A variety of changes in hormonal/neurohormonal systems and brain circuits are involved in the maternal behavior. Hormones, neuropeptides, and neurotransmitters involved in maternal behavior act via G-protein-coupled receptors, many of which in turn activate plasma membrane enzymes including phospholipase C (PLC) β isoforms. In this study, we examined the effect of PLCβ1 knockout (KO) on maternal behavior. There was little difference between PLCβ1-KO and wild-type (WT) dams in the relative time spent in maternal behavior during the period between 24 h prepartum and 12 h postpartum (−24 h ∼ PPH 12). After PPH 18, however, PLCβ1-KO dams neglected their pups so that they all died in 2–3 days. In the pup retrieval test, latency was not different during the period within PPH 12, but after PPH 18, PLCβ1-KO dams could not finish pup retrieval in a given time. During both periods, FosB expression in the nucleus accumbens (NAcc) of PLCβ1-KO dams was significantly lower than WT, but not different in the medial preoptic area (mPOA). Given that mPOA activity is required for initiation of maternal behavior, and that NAcc is known to be involved in maternal motivation and maintenance of maternal behavior, our results suggest that PLCβ1 signaling is essential for transition from the onset to maintenance phase of maternal behavior.