1. Suppressed prefrontal neuronal firing variability and impaired social representation in IRSp53-mutant mice
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Woohyun Kim, Jae Jin Shin, Yu Jin Jeong, Kyungdeok Kim, Jung Won Bae, Young Woo Noh, Seungjoon Lee, Woochul Choi, Se-Bum Paik, Min Whan Jung, Eunee Lee, and Eunjoon Kim
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firing variability ,IRSp53 ,medial prefrontal cortex ,social behavior ,BAIAP2 ,social deficit ,Medicine ,Science ,Biology (General) ,QH301-705.5 - Abstract
Social deficit is a major feature of neuropsychiatric disorders, including autism spectrum disorders, schizophrenia, and attention-deficit/hyperactivity disorder, but its neural mechanisms remain unclear. Here, we examined neuronal discharge characteristics in the medial prefrontal cortex (mPFC) of IRSp53/Baiap2-mutant mice, which show social deficits, during social approach. We found a decrease in the proportion of IRSp53-mutant excitatory mPFC neurons encoding social information, but not that encoding non-social information. In addition, the firing activity of IRSp53-mutant neurons was less differential between social and non-social targets. IRSp53-mutant excitatory mPFC neurons displayed an increase in baseline neuronal firing, but decreases in the variability and dynamic range of firing as well as burst firing during social and non-social target approaches compared to wild-type controls. Treatment of memantine, an NMDA receptor antagonist that rescues social deficit in IRSp53-mutant mice, alleviates the reduced burst firing of IRSp53-mutant pyramidal mPFC neurons. These results suggest that suppressed neuronal activity dynamics and burst firing may underlie impaired cortical encoding of social information and social behaviors in IRSp53-mutant mice.
- Published
- 2022
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