Effects of Npas4 deficiency on anxiety, depression-like, cognition and sociability behaviour

•Npas4−/− mice show decreased anxiety behaviour in the elevated zero maze.•Npas4−/+ mice show increased depression-like behaviour in forced swim test.•Npas4−/+ mice show impaired spatial recognition memory in the Y-maze.

The transcription factor neuronal PAS domain-containing protein 4 (Npas4), which regulates the formation of inhibitory synapses on excitatory neurons, has been suggested as a candidate gene for neurological and psychiatric conditions such as bipolar depression, autism spectrum and cognitive disorders. A mouse model of Npas4 deficiency has been developed to investigate any role in these disorders. Behavioural characterisation of Npas4−/−, Npas4+/− and Npas4+/+ mice has been conducted using the open field, elevated zero maze (EZM), Y-maze, sociability test and forced swim test (FST) to investigate a range of behaviours. Npas4−/− mice spent more time in the open arm of the EZM than other genotypes, suggesting decreased anxiety-like behaviour. Npas4+/− mice, however, were more immobile in the FST than other genotypes, suggesting increased depression-like behaviour, and also showed impaired spatial recognition memory in the Y-maze. There were no differences between genotype in social behaviour. These results suggest that differential levels of Npas4 expression in the brain may regulate anxiety, depression and cognition related disorders.