Characterization of prefrontal neuronal activity of IRSp53-mutant mice with social deficits

Abstract

Social deficit is a prominent symptom of certain neuropsychiatric disorders, including autism spectrum disorders, schizophrenia, and attention-deficit/hyperactivity disorder. However, the neural mechanism underlying social deficit remains unclear. In this study, we characterized the firing and encoding dynamics of neurons in the medial prefrontal cortex (mPFC), a region that is strongly associated with social higher cognitive function, of IRSp53-mutant mice with social deficits. While mPFC excitatory neurons of IRSp53-mutant mice, compared to that of the wild-type controls, exhibited an increase in firing rate during rest, during social and non-social target approaches, they displayed comparable firing rate, with decreases in spike variability, firing-rate range, and burst firing. Consequently, the firing activity of IRSp53-mutant mPFC excitatory neurons was less differential between social and non-social targets. Additionally, IRSp53-KO mice displayed a reduction in the proportion of social information coding neurons, but a normal proportion of non-social information coding neurons in the mPFC. Paramacological restoration of NMDAR function via memantine, which normalizes social deficit in IRSp53-mutant mice, increases the suppressed burst firing in IRSp53-mutant mPFC pyramidal neurons, in vitro. Collectively, these results suggest that a reduction in the dynamics of neuronal activity may be associated with impairments in cortical encoding of social information and, subsequently, social behaviors in IRSp53-mutant mice.