Suppressed prefrontal neuronal firing variability and impaired social representation in IRSp53-mutant mice

  1. Woohyun Kim
  2. Jae Jin Shin
  3. Yu Jin Jeong
  4. Kyungdeok Kim
  5. Jung Won Bae
  6. Young Woo Noh
  7. Seungjoon Lee
  8. Woochul Choi
  9. Se-Bum Paik
  10. Min Whan Jung  Is a corresponding author
  11. Eunee Lee  Is a corresponding author
  12. Eunjoon Kim  Is a corresponding author
  1. Korea Advanced Institute of Science and Technology, Republic of Korea
  2. 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.

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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

  1. Woohyun Kim

    Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea
    Competing interests
    No competing interests declared.
  2. Jae Jin Shin

    Center for Synaptic Brain Dysfunctions, Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea
    Competing interests
    No competing interests declared.
  3. Yu Jin Jeong

    Department of Anatomy, Yonsei University, Seoul, Republic of Korea
    Competing interests
    No competing interests declared.
  4. Kyungdeok Kim

    Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0003-6957
  5. Jung Won Bae

    Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea
    Competing interests
    No competing interests declared.
  6. Young Woo Noh

    Center for Synaptic Brain Dysfunctions, Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8280-2717
  7. Seungjoon Lee

    Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea
    Competing interests
    No competing interests declared.
  8. Woochul Choi

    Department of Bio and Brain Engineering, Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea
    Competing interests
    No competing interests declared.
  9. Se-Bum Paik

    Department of Bio and Brain Engineering, Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4078-305X
  10. Min Whan Jung

    Center for Synaptic Brain Dysfunctions, Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea
    For correspondence
    mwjung@kaist.ac.kr
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4145-600X
  11. Eunee Lee

    Department of Anatomy, Yonsei University, Seoul, Republic of Korea
    For correspondence
    obsee93@gmail.com
    Competing interests
    No competing interests declared.
  12. Eunjoon Kim

    Center for Synaptic Brain Dysfunctions, Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea
    For correspondence
    kime@kaist.ac.kr
    Competing interests
    Eunjoon Kim, Reviewing editor, eLife.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5518-6584

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.

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).

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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  1. Woohyun Kim
  2. Jae Jin Shin
  3. Yu Jin Jeong
  4. Kyungdeok Kim
  5. Jung Won Bae
  6. Young Woo Noh
  7. Seungjoon Lee
  8. Woochul Choi
  9. Se-Bum Paik
  10. Min Whan Jung
  11. Eunee Lee
  12. Eunjoon Kim
(2022)
Suppressed prefrontal neuronal firing variability and impaired social representation in IRSp53-mutant mice
eLife 11:e74998.
https://doi.org/10.7554/eLife.74998

Share this article

https://doi.org/10.7554/eLife.74998

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