Cell-Type-Specific <i>Shank2</i> Deletion in Mice Leads to Differential Synaptic and Behavioral Phenotypes

Kim, Ryunhee,Kim, Jihye,Chung, Changuk,Ha, Seungmin,Lee, Seungjoon,Lee, Eunee,Yoo, Ye-Eun,Kim, Woohyun,Shin, Wangyong,Kim, Eunjoon Society for Neuroscience 2018 The Journal of neuroscience Vol.38 No.17

<P>Shank2 is an excitatory postsynaptic scaffolding protein implicated in synaptic regulation and psychiatric disorders including autism spectrum disorders. Conventional Shank2-mutant (Shank2(-/-)) mice display several autistic-like behaviors, including social deficits, repetitive behaviors, hyperactivity, and anxiety-like behaviors. However, cell-type-specific contributions to these behaviors have remained largely unclear. Here, we deleted Shank2 in specific cell types and found that male mice lacking Shank2 in excitatory neurons (CaMKII-Cre;Shank2(fl/fl)) show social interaction deficits and mild social communication deficits, hyperactivity, and anxiety-like behaviors. In particular, male mice lacking Shank2 in GABAergic inhibitory neurons (Viaat-Cre;Shank2(fl/fl)) display social communication deficits, repetitive self-grooming, and mild hyperactivity. These behavioral changes were associated with distinct changes in hippocampal and striatal synaptic transmission in the two mouse lines. These results indicate that cell-type-specific deletions of Shank2 in mice lead to differential synaptic and behavioral abnormalities.</P>

Lrfn2-Mutant Mice Display Suppressed Synaptic Plasticity and Inhibitory Synapse Development and Abnormal Social Communication and Startle Response

Li, Yan,Kim, Ryunhee,Cho, Yi Sul,Song, Woo Seok,Kim, Doyoun,Kim, Kyungdeok,Roh, Junyeop Daniel,Chung, Changuk,Park, Hanwool,Yang, Esther,Kim, Soo-Jeong,Ko, Jaewon,Kim, Hyun,Kim, Myoung-Hwan,Bae, Yong- Society for Neuroscience 2018 The Journal of neuroscience Vol.38 No.26

<P>SALM1 (SALM (synaptic adhesion-like molecule), also known as LRFN2 (leucine rich repeat and fibronectin type III domain containing), is a postsynaptic density (PSD)-95-interacting synaptic adhesion molecule implicated in the regulation of NMDA receptor (NMDAR) clustering largely based on in vitro data, although its in vivo functions remain unclear. Here, we found that mice lacking SALM1/LRFN2 (Lrfn2(-/-) mice) show a normal density of excitatory synapses but altered excitatory synaptic function, including enhanced NMDAR-dependent synaptic transmission but suppressed NMDAR-dependent synaptic plasticity in the hippocampal CA1 region. Unexpectedly, SALM1expression was detected in both glutamatergic and GABAergic neurons and Lrfn2(-/-) CA1 pyramidal neurons showed decreases in the density of inhibitory synapses and the frequency of spontaneous inhibitory synaptic transmission. Behaviorally, ultrasonic vocalization was suppressed in Lrfn2(-/-) pups separated from their mothers and acoustic startle was enhanced, but locomotion, anxiety-like behavior, social interaction, repetitive behaviors, and learning and memory were largely normal in adult male Lrfn2(-/-) mice. These results suggest that SALM1/LRFN2 regulates excitatory synapse function, inhibitory synapse development, and social communication and startle behaviors in mice.</P>

멀티 코어 환경에서 오류 주입 공격에 안전한 RSA-CRT

송창욱(Changuk Song),김한얼(Hanur Kim),김지혜(Jihye Kim) 한국정보과학회 2012 한국정보과학회 학술발표논문집 Vol.39 No.2C

Association between Estrogen Receptor Gene Polymorphisms and Depression in Post-Menopausal Women: A Preliminary Study

JungJin Kim,ChiUn Pae,MiRan Kim,JungAh Min,KyungHee Kim,ChangUk Lee,Chul Lee,InHo Paik 대한신경정신의학회 2010 PSYCHIATRY INVESTIGATION Vol.7 No.3

Post-menopausal women experience variable biological and psychological changes. The effect of reduced levels of estrogen can effect on post-menopausal depression. Estrogen triggers physiological responses by binding to the estrogen receptor (ER). Two subtypes of ER, ERa and ERb are now known. We investigated the significance of ERa and ERb polymorphisms and post-menopasal depression in this study. Forty three women with post-menopausal depression and 63 post-menopausal women without depression as normal controls were recruited. Polymerase chain reaction-restriction fragment length polymorphism method was used to investigate genotypes of ERa and ERb polymorphisms. Genotypes of PvuII and XbaI polymorphism of ERa receptor were significantly different in patients with post-menopausal depression comparing with controls. Genotypes of ERb did not show association with post-menopausal depression. Our study showed that ERa receptor polymorphism had an association with depression in post-menopausal women. It suggests that investigation of ER genes and their functions might be important for understanding pathophysilogical mechanism of post-menopausal depression.

대드론 전투 시 사격할당을 위한 최적화 모형 연구

김창욱(Changuk Kim),조남석(Namsuk Cho) 대한산업공학회 2020 대한산업공학회지 Vol.46 No.5

학습동기유형 분석을 통한 e러닝 시장의 개척과 확산 방안에 관한 연구

김남국(Namkuk Kim),이준기(Zoonki Lee),정창욱(Changuk Jung),김종혁(Jonghyuk Kim) 한국전자거래학회 2013 한국전자거래학회지 Vol.18 No.3

본 연구는 국내 e러닝 시장을 개척한 기업인 크레듀가 어떻게 시장 진입 기회를 포착하였으며 핵심역량 강화와 함께 어떻게 다각화를 추진하였는가를 실제 사례와 함께 학습자의 e러닝 학습동기유형을 분석하여 살펴보고 기업 차원에서 여러 가지 e러닝 기법들이 어떻게 발전해왔고, 또한 이것을 적용하는 방식에서 어떠한 대응이 필요했는지를 조사하였다. e러닝 시장에서 치열한 경쟁이 펼쳐지고 있는 가운데, 크레듀는 핵심역량을 유지하고 강화하기 위해 고객과 적극적인 의사소통 채널을 만들어 핵심 사업 분야에 대한 집중적인 투자를 단행하면서 학습자의 개인적 특성을 파악하고 학습동기유형에 대한 모델을 만들어 보다 모험적이고 실험적인 제품과 서비스를 출시해 e러닝 발전에 기여했으며 경쟁 우위를 유지할 수 있었다. 본 연구는 소비자의 e러닝 학습동기유형을 분류한 선도적인 연구일 뿐만 아니라 성공한 e러닝 기업의 사례를 통한 e러닝 시장의 개척과 확산 방안에 관한 기법을 소개함으로써 실무적인 측면에서 그 가치가 높을 것으로 기대한다. The study investigated how did Credu pioneer Korean e-Learning market and reinforce their core competencies and how did they promote business diversification analyzing type of learning motives and examining Credu real cases. Under the fierce competition in the current e-Learning market, Credu has maintained their core competencies and strengthened an active communication channels with customers with focusing on investment to core businesses. Credu has introduced more adventurous and challenging products and services with creating a new model for the types of learning motives. This study could introduce the new perspective about the type of learning motives in e-Learning area. Also, the case study of successful e-Learning company, Credu, could contribute to make more spread e-Learning market techniques in this field in practice.

<i>Shank3</i> -mutant mice lacking exon 9 show altered excitation/inhibition balance, enhanced rearing, and spatial memory deficit

Lee, Jiseok,Chung, Changuk,Ha, Seungmin,Lee, Dongmin,Kim, Do-Young,Kim, Hyun,Kim, Eunjoon Frontiers Media S.A. 2015 Frontiers in cellular neuroscience Vol.9 No.-

<P>Shank3 is a postsynaptic scaffolding protein implicated in synapse development and autism spectrum disorders. The <I>Shank3</I> gene is known to produce diverse splice variants whose functions have not been fully explored. In the present study, we generated mice lacking <I>Shank3</I> exon 9 (<I>Shank3</I><SUP>Δ<I>9</I></SUP> mice), and thus missing five out of 10 known Shank3 splice variants containing the N-terminal ankyrin repeat region, including the longest splice variant, Shank3a. Our X-gal staining results revealed that Shank3 proteins encoded by exon 9-containing splice variants are abundant in upper cortical layers, striatum, hippocampus, and thalamus, but not in the olfactory bulb or cerebellum, despite the significant Shank3 mRNA levels in these regions. The hippocampal CA1 region of <I>Shank3</I><SUP>Δ<I>9</I></SUP> mice exhibited reduced excitatory transmission at Schaffer collateral synapses and increased frequency of spontaneous inhibitory synaptic events in pyramidal neurons. In contrast, prelimbic layer 2/3 pyramidal neurons in the medial prefrontal cortex displayed decreased frequency of spontaneous inhibitory synaptic events, indicating alterations in the ratio of excitation/inhibition (E/I ratio) in the <I>Shank3</I><SUP>Δ<I>9</I></SUP> brain. These mice displayed a mild increase in rearing in a novel environment and mildly impaired spatial memory, but showed normal social interaction and repetitive behavior. These results suggest that ankyrin repeat-containing Shank3 splice variants are important for E/I balance, rearing behavior, and spatial memory.</P>

Genetic Association of CHRNB3 and CHRNA6 Gene Polymorphisms with Nicotine Dependence Syndrome Scale in Korean Population

WangYoun Won,ByungLae Park,SamWook Choi,LyoungHyo Kim,Min Kwon,JaeHwa Kim,ChangUk Lee,HyoungDoo Shin,DaiJin Kim 대한신경정신의학회 2014 PSYCHIATRY INVESTIGATION Vol.11 No.3

Objective-Cholinergic nicotinic receptor (CHRN) gene family has been known to mediate the highly additive effects of nicotine in the body, and implicated nicotine dependence (ND) and related phenotypes. Previous studies have found that CHRNA6-CHRNB3 cluster polymorphisms were significantly associated with the risk of ND and various tobacco behaviors. The aim of study was to evaluate the genetic association of CHRNB3 and CHRNA6 polymorphisms with the risk of ND based on the Fagerstrom Test for Nicotine Dependence (FTND) score and five subscales of nicotine dependence syndrome scale (NDSS) in Korean population. Methods-Six SNPs in CHRNA6-CHRNB3 cluster were analyzed in 576 Korean subjects. Association analysis using logistic models and regression analysis with NDSS were performed. Results-There was no association in the case-control analysis, whereas all six SNPs were significantly associated with drive factor among NDSS in subgroup based on the FTND score. CHRNB3 rs4954 and CHRNA6 rs16891604 showed significant associations with NDSSF1 (drive) in dominant models among moderate to severe ND among smokers after correction (pcorr=0.02 and 0.001, respectively), whereas other four SNPs showed significant associations among mild ND after correction (pcorr=0.03-0.02 in dominant model). Conclusion-This study showed that the genetic influence of CHRNB3-CHRNA6 cluster polymorphisms are found in a ND endophenotype (drive) using NDSS subscales, rather than the risk of ND in Korean population. Our findings might be the first report for the association of CHRNB3-CHRNA6 cluster with ND-related phenotypes in Korean and might offer an approach to elucidating the molecular mechanisms of ND and ND-related phenotypes.

Cerebellar Shank2 Regulates Excitatory Synapse Density, Motor Coordination, and Specific Repetitive and Anxiety-Like Behaviors

Ha, Seungmin,Lee, Dongwon,Cho, Yi Sul,Chung, Changuk,Yoo, Ye-Eun,Kim, Jihye,Lee, Jiseok,Kim, Woohyun,Kim, Hyosang,Bae, Yong Chul,Tanaka-Yamamoto, Keiko,Kim, Eunjoon Society for Neuroscience 2016 The Journal of neuroscience Vol.36 No.48

<P>Shank2 is a multidomain scaffolding protein implicated in the structural and functional coordination of multiprotein complexes at excitatory postsynaptic sites as well as in psychiatric disorders, including autism spectrum disorders. While Shank2 is strongly expressed in the cerebellum, whether Shank2 regulates cerebellar excitatory synapses, or contributes to the behavioral abnormalities observed in Shank2(-/-) mice, remains unexplored. Here we show that Shank2(-/-) mice show reduced excitatory synapse density in cerebellar Purkinje cells in association with reduced levels of excitatory postsynaptic proteins, including GluD2 and PSD-93, and impaired motor coordination in the Erasmus test. Shank2 deletion restricted to Purkinje cells (Pcp2-Cre; Shank2(fl/fl) mice) leads to similar reductions in excitatory synapse density, synaptic protein levels, and motor coordination. Pcp2-Cre; Shank2(fl/fl) mice do not recapitulate autistic-like behaviors observed in Shank2(-/-) mice, such as social interaction deficits, altered ultrasonic vocalizations, repetitive behaviors, and hyperactivity. However, Pcp2-Cre; Shank2(fl/fl) mice display enhanced repetitive behavior in the hole-board test and anxiety-like behavior in the light-dark test, which are not observed in Shan2(-/-) mice. These results implicate Shank2 in the regulation of cerebellar excitatory synapse density, motor coordination, and specific repetitive and anxiety-like behaviors.</P>

교량의 하중실험과 과하중 확률계산을 통한 내하력 평가 에 대한 연구

김두환,유창욱 서울産業大學校 2005 논문집 Vol.54 No.2

We are currently conducting the static and dynamic load test for evaluating bridge loading carrying capacity. Using the rating factors, there are many attempts to make a connection between rating factors and probability concept. In this paper, the probability of overload is computed to apply Monte-Carlo Simulation by using live load from WIM. And new rate of bridge inspection is evaluated by the. probability of overload and visual inspection.