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.
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.
Metrics
-
- 1,310
- views
-
- 194
- downloads
-
- 4
- citations
Views, downloads and citations are aggregated across all versions of this paper published by eLife.
Download links
A two-part list of links to download the article, or parts of the article, in various formats.
Downloads (link to download the article as PDF)
Open citations (links to open the citations from this article in various online reference manager services)
Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)
Suppressed prefrontal neuronal firing variability and impaired social representation in IRSp53-mutant mice
eLife 11:e74998.
https://doi.org/10.7554/eLife.74998
Further reading
-
- Neuroscience
Since its inception, the concept of neurodiversity has been defined in a number of different ways, which can cause confusion among those hoping to educate themselves about the topic. Learning about neurodiversity can also be challenging because there is a lack of well-curated, appropriately contextualized information on the topic. To address such barriers, we present an annotated reading list that was developed collaboratively by a neurodiverse group of researchers. The nine themes covered in the reading list are: the history of neurodiversity; ways of thinking about neurodiversity; the importance of lived experience; a neurodiversity paradigm for autism science; beyond deficit views of ADHD; expanding the scope of neurodiversity; anti-ableism; the need for robust theory and methods; and integration with open and participatory work. We hope this resource can support readers in understanding some of the key ideas and topics within neurodiversity, and that it can further orient researchers towards more rigorous, destigmatizing, accessible, and inclusive scientific practices.
-
- Neuroscience
Brain rhythms can facilitate neural communication for the maintenance of brain function. Beta rhythms (13–35 Hz) have been proposed to serve multiple domains of human ability, including motor control, cognition, memory, and emotion, but the overarching organisational principles remain unknown. To uncover the circuit architecture of beta oscillations, we leverage normative brain data, analysing over 30 hr of invasive brain signals from 1772 channels from cortical areas in epilepsy patients, to demonstrate that beta is the most distributed cortical brain rhythm. Next, we identify a shared brain network from beta-dominant areas with deeper brain structures, like the basal ganglia, by mapping parametrised oscillatory peaks to whole-brain functional and structural MRI connectomes. Finally, we show that these networks share significant overlap with dopamine uptake as indicated by positron emission tomography. Our study suggests that beta oscillations emerge in cortico-subcortical brain networks that are modulated by dopamine. It provides the foundation for a unifying circuit-based conceptualisation of the functional role of beta activity beyond the motor domain and may inspire an extended investigation of beta activity as a feedback signal for closed-loop neurotherapies for dopaminergic disorders.
