Suppressed prefrontal neuronal firing variability and impaired social representation in IRSp53-mutant mice
- Korea Advanced Institute of Science and Technology, Republic of Korea
- Yonsei University, Republic of Korea
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.
Data availability
Source Data files have been provided for all figures (except for Figure 1 - figure supplement 1, Figure 3, and Figure 3 - figure supplement 1).
Article and author information
Author details
Funding
National Research Foundation of Korea (NRF-2022M3E5E8018388)
- Eunee Lee
Ministry of Health and Welfare (KHDI HI21C1659)
- Eunee Lee
National Research Foundation of Korea (NRF-2019R1A2C4069863)
- Se-Bum Paik
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Xiang Yu, Peking University, China
Ethics
Animal experimentation: Mice were maintained according to the Animal Research Requirements of Korea Advanced Institute of Science and Technology (KAIST). All experiments were conducted with approval from the Committee on Animal Research at KAIST (approval number KA2020-94).
Version history
- Received: October 26, 2021
- Preprint posted: November 19, 2021 (view preprint)
- Accepted: October 31, 2022
- Accepted Manuscript published: November 1, 2022 (version 1)
- Version of Record published: November 14, 2022 (version 2)
Copyright
© 2022, Kim et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Suppressed prefrontal neuronal firing variability and impaired social representation in IRSp53-mutant mice
eLife 11:e74998.
https://doi.org/10.7554/eLife.74998
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