Neural circuit pathology driven by Shank3 mutation disrupts social behaviors

Kim, Sunwhi; Kim, Yong-Eun; Song, Inuk; Ujihara, Yusuke; Kim, Namsoo; Jiang, Yong‐Hui; Yin, Henry H.; Lee, Tae‐Ho; Kim, Il Hwan

doi:10.1016/j.celrep.2022.110906

Cited by 29 publications

(38 citation statements)

References 87 publications

(132 reference statements)

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“…Stimulation of the VTA neurons also reduced the stress-induced anxiety. Similarly, network connections between prefrontal cortex and the basolateral amygdala have been studied as models of social dysfunction in autism [37]. The absence of social behavior deficits after UCMS in our experimental design (Figures 1, 9) may be an important clue as to network connections involving the VTA in the anxiety response.…”

Section: Discussionmentioning

confidence: 75%

Persistent Hypersomnia Following Repetitive Mild Experimental Traumatic Brain Injury: Roles of Chronic Stress and Sex Differences

Portillo

Kim

et al. 2022

Preprint

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Traumatic brain injury (TBI) is often more complicated than a single head injury. An extreme example of this point may be military service members who experience a spectrum of exposures over a prolonged period under stressful conditions. Understanding the effects of complex exposures can support proper evaluation and care for patients experiencing persistent symptoms. We designed a longitudinal series of non-invasive procedures in adult mice to evaluate the effects of prolonged mild exposures. We assessed anxiety, depression, and sleep-wake dysfunction as symptoms that can impact long term outcomes after mild TBI. Unpredictable chronic mild stress (UCMS) was generated from a variable sequence of environmental stressors distributed within each of 21 days. Subsequently, mice received a mild blast combined with closed-head mild TBI on five days at 24-hour intervals. TBI components were either five linear force impacts, or a novel alternating repetitive mild TBI (Ar-mTBI) model of linear and rotational (CHIMERA) impacts over five days to produce diffuse pathology. In males and females, UCMS induced anxiety without depressive behavior. Persistent hypersomnia, specifically increased sleep during the active dark period, was found through 6-12 month time points in male mice receiving UCMS with repetitive blast plus TBI events, or surprisingly after UCMS alone. Sleep-wake dysfunction was not found with TBI events alone and was not found in females under any conditions. These results identify prolonged stress and sex differences as important considerations for sleep-wake dysfunction. Furthermore, this reproducible hypersomnia is similar to excessive daytime sleepiness reported in patients, which may inform treatments.

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Section: Discussionmentioning

confidence: 75%

Persistent Hypersomnia Following Repetitive Mild Experimental Traumatic Brain Injury: Roles of Chronic Stress and Sex Differences

Portillo

Kim

et al. 2022

Preprint

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“…Given that GCaMP viral injection and GRIN lens/baseplate implantation have been complete, below is the protocol for conducting an RSA experiment with simultaneous Ca 2+ imaging. Detailed protocols for viral injection and GRIN lens/baseplate implantation can be found in these references: ( Kim et al., 2015 , 2020 , 2022 ; Liang et al., 2018 ; Kennedy et al., 2020 ). For a step-by-step protocol for these processes, please refer to ( Carrier-Ruiz et al., 2021 ).…”

Section: Step-by-step Methods Detailsmentioning

confidence: 99%

“…Estimated time required for optogenetic experiment with RSA is about 9 days, including 3 days of handling, 3 days of habituation, 1 day of baseline RSA test, 1 day of RSA with optic stimulation in RSA, and 1 day of optic stimulation without social stimulus. For detailed experimental procedures, see: ( Kim et al., 2020 , 2022 ). In the current section, how to connect RSA with optogenetic stimulation system is explained.…”

Section: Step-by-step Methods Detailsmentioning

confidence: 99%

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Simultaneous analysis of social behaviors and neural responses in mice using round social arena system

Kim¹,

Kim²,

Kim³

2022

STAR Protocols

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“…Zhou et al (2019) found SHANK3 mutant rhesus monkeys with autism-related symptoms showed abnormal connections in brain function, particularly inadequate long connections between the default mode network, including between the posterior cingulate gyrus, medial prefrontal cortex (mPFC) and motor areas [16]. Kim et al (2022) proposed that ASD patients showed higher mPFC-amygdala functional connectivity at static and dynamic levels than the control group, and the connectivity was specific [17]. Fernandez et al (2019) proposed that inadequate connectivity was the root cause of behavioral defects and may be the cause of brain diseases such as autism or schizophrenia [18].…”

Section: Introductionmentioning

confidence: 99%

Identification of Young High-Functioning Autism Individuals Based on Functional Connectome Using Graph Isomorphism Network: A Pilot Study

Yang

Jin

et al. 2022

Brain Sciences

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Accumulated studies have determined the changes in functional connectivity in autism spectrum disorder (ASD) and spurred the application of machine learning for classifying ASD. Graph Neural Network provides a new method for network analysis in brain disorders to identify the underlying network features associated with functional deficits. Here, we proposed an improved model of Graph Isomorphism Network (GIN) that implements the Weisfeiler-Lehman (WL) graph isomorphism test to learn the graph features while taking into account the importance of each node in the classification to improve the interpretability of the algorithm. We applied the proposed method on multisite datasets of resting-state functional connectome from Autism Brain Imaging Data Exchange (ABIDE) after stringent quality control. The proposed method outperformed other commonly used classification methods on five different evaluation metrics. We also identified salient ROIs in visual and frontoparietal control networks, which could provide potential neuroimaging biomarkers for ASD identification.

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Neural circuit pathology driven by Shank3 mutation disrupts social behaviors

Cited by 29 publications

References 87 publications

Persistent Hypersomnia Following Repetitive Mild Experimental Traumatic Brain Injury: Roles of Chronic Stress and Sex Differences

Persistent Hypersomnia Following Repetitive Mild Experimental Traumatic Brain Injury: Roles of Chronic Stress and Sex Differences

Simultaneous analysis of social behaviors and neural responses in mice using round social arena system

Identification of Young High-Functioning Autism Individuals Based on Functional Connectome Using Graph Isomorphism Network: A Pilot Study

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