AMPA receptor exchange underlies transient memory destabilization on retrieval

Hong, Ingie,Kim, Jeongyeon,Kim, Jihye,Lee, Sukwon,Ko, Hyoung-Gon,Nader, Karim,Kaang, Bong-Kiun,Tsien, Richard W.,Choi, Sukwoo National Academy of Sciences 2013 PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF Vol.110 No.20

<P>A consolidated memory can be transiently destabilized by memory retrieval, after which memories are reconsolidated within a few hours; however, the molecular substrates underlying this destabilization process remain essentially unknown. Here we show that at lateral amygdala synapses, fear memory consolidation correlates with increased surface expression of calcium-impermeable AMPA receptors (CI-AMPARs), which are known to be more stable at the synapse, whereas memory retrieval induces an abrupt exchange of CI-AMPARs to calcium-permeable AMPARs (CP-AMPARs), which are known to be less stable at the synapse. We found that blockade of either CI-AMPAR endocytosis or NMDA receptor activity during memory retrieval, both of which blocked the exchange to CP-AMPARs, prevented memory destabilization, indicating that this transient exchange of AMPARs may underlie the transformation of a stable memory into an unstable memory. These newly inserted CP-AMPARs gradually exchanged back to CI-AMPARs within hours, which coincided with the course of reconsolidation. Furthermore, blocking the activity of these newly inserted CP-AMPARs after retrieval impaired reconsolidation, suggesting that they serve as synaptic “tags” that support synapse-specific reconsolidation. Taken together, our results reveal unexpected physiological roles of CI-AMPARs and CP-AMPARs in transforming a consolidated memory into an unstable memory and subsequently guiding reconsolidation.</P>

Extinction of cued fear memory involves a distinct form of depotentiation at cortical input synapses onto the lateral amygdala

Hong, Ingie,Song, Beomjong,Lee, Sukwon,Kim, Jihye,Kim, Jeongyeon,Choi, Sukwoo Blackwell Publishing Ltd 2009 The European journal of neuroscience Vol.30 No.11

<P>Abstract</P><P>The amygdala is known to be a critical storage site of conditioned fear memory. Among the two major pathways to the lateral amygdala (LA), the cortical pathway is known to display a presynaptic long-term potentiation which is occluded with fear conditioning. Here we show that fear extinction results in a net depression of conditioning-induced potentiation at cortical input synapses onto the LA (C-LA synapses). Fear conditioning induced a significant potentiation of excitatory postsynaptic currents at C-LA synapses compared with naïve and unpaired controls, whereas extinction apparently reversed this potentiation. Paired-pulse low-frequency stimulation (pp-LFS) induced synaptic depression in the C-LA pathway of fear-conditioned rats, but not in naïve or unpaired controls, indicating that the pp-LFS-induced depression is specific to associative learning-induced changes (pp-LFS-induced depotentiation<SUB><I>ex vivo</I></SUB>). Importantly, extinction occluded pp-LFS-induced depotentiation<SUB><I>ex vivo</I></SUB>, suggesting that extinction shares some mechanisms with the depotentiation. pp-LFS-induced depotentiation<SUB><I>ex vivo</I></SUB> required NMDA receptor (NMDAR) activity, consistent with a previous finding that blockade of amygdala NMDARs impaired fear extinction. In addition, pp-LFS-induced depotentiation<SUB><I>ex vivo</I></SUB> required activity of group II metabotropic glutamate receptors (mGluRs), known to be present at presynaptic terminals, but not AMPAR internalization, consistent with a presynaptic mechanism for pp-LFS-induced depotentiation<SUB><I>ex vivo</I></SUB>. This result is in contrast with another form of <I>ex vivo</I> depotentiation in the thalamic pathway that requires both group I mGluR activity and AMPAR internalization. We thus suggest that extinction of conditioned fear involves a distinct form of depotentiation at C-LA synapses, which depends upon both NMDARs and group II mGluRs.</P>

인공땀으로 출력한 인공지문의 균질성 평가

홍인기(Ingi Hong),홍성욱(Sungwook Hong) 한국분석과학회 2015 분석과학 Vol.28 No.1

지능형교통시스템의 전력선 통신(PLC) 적용방안에 관한 연구

홍인기(Hong Ingi),이봉규(Lee Bong-Gyou),류승기(Ryu Seung-Ki) 대한전기학회 2005 대한전기학회 학술대회 논문집 Vol.2005 No.7

Long-term neural correlates of reversible fear learning in the lateral amygdala.

An, Bobae,Hong, Ingie,Choi, Sukwoo The Society 2012 The Journal of neuroscience Vol.32 No.47

<P>Fear conditioning and extinction are behavioral models that reflect the association and dissociation of environmental cues to aversive outcomes, both known to involve the lateral amygdala (LA). Accordingly, responses of LA neurons to conditioned stimuli (CS) increase after fear conditioning and decrease partially during extinction. However, the long-term effects of repeated fear conditioning and extinction on LA neuronal firing have not been explored. Here we show, using stable, high signal-to-noise ratio single-unit recordings, that the ensemble activity of all recorded LA neurons correlates tightly with conditioned fear responses of rats in a conditioning/extinction/reconditioning paradigm spanning 3 d. This CS-evoked ensemble activity increased after conditioning, decreased after extinction, and was repotentiated after reconditioning. Cell-by-cell analysis revealed that among the LA neurons that displayed potentiated responses after initial fear conditioning, some exhibited weakened CS responses after extinction (extinction-susceptible), whereas others remained potentiated (extinction-resistant). The majority of extinction-susceptible neurons exhibited strong potentiation after reconditioning, suggesting that this distinct subpopulation (reversible fear neurons) encodes updated CS-unconditioned stimulus (US) association strength. Interestingly, these reversible fear neurons displayed larger, more rapid potentiation during reconditioning compared with the initial conditioning, providing a neural correlate of savings after extinction. In contrast, the extinction-resistant fear neurons did not show further increases after reconditioning, suggesting that this subpopulation encodes persistent fear memory representing the original CS-US association. This longitudinal report on LA neuronal activity during reversible fear learning suggests the existence of distinct populations encoding various facets of fear memory and provides insight into the neuronal mechanisms of fear memory modulation.</P>

Group I mGluR-dependent depotentiation in the lateral amygdala does not require the removal of calcium-permeable AMPA receptors

Park, Kyungjoon,Song, Sukwoon,Hong, Ingie,Song, Beomjong,Kim, Jeongyeon,Park, Sungmo,Lee, Junuk,Song, Sangho,An, Bobae,Kim, Jihye,Lee, C. Justin,Shin, Ki Soon,Choi, Sukwoo,Lee, Sukwon Frontiers Media S.A. 2014 Frontiers in Behavioral Neuroscience Vol.8 No.-

<P>There is conflicting evidence regarding whether calcium-permeable receptors are removed during group I mGluR-mediated synaptic depression. In support of this hypothesis, AMPAR rectification, a correlative index of the synaptic expression of GluA2-lacking calcium–permeable AMPARs (CP-AMPARs), is known to decrease after the induction of several types of group I mGluR-mediated long-term depression (LTD), suggesting that a significant proportion of synaptic CP-AMPARs is removed during synaptic depression. We have previously demonstrated that fear conditioning-induced synaptic potentiation in the lateral amygdala is reversed by group 1 mGluR-mediated depotentiation. Here, we examined whether CP-AMPARs are removed by mGluR1-mediated depotentiation of fear conditioning-induced synaptic potentiation. The synaptic expression of CP-AMPARs was negligible before, increased significantly 12 h after, and returned to baseline 48 h after fear conditioning, as evidenced by the changes in the sensitivity of lateral amygdala synaptic responses to NASPM. Importantly, the sensitivity to NASPM was not altered after induction of depotentiation. Our findings, together with previous results, suggest that the removal of CP-AMPARs is not required for the depotentiation of fear conditioning-induced synaptic potentiation at lateral amygdala synapses.</P>

Analysis of Major Industrial Accidents in Chemical Facilities Based on Human Error Classification Framework

Jungchul Park,Seung-Kwon Hong,Jongbae Baek,Ingie Hong,Keun Won Lee,Woosub Han 대한인간공학회 2013 대한인간공학회 학술대회논문집 Vol.2013 No.10

Objective: The aim of this study is to develop a human error classification framework for chemical facilities and to apply it to major industrial accidents in chemical facilities in Korea. Background: Human errors can be classified with various criteria such as human information processing procedure by which the error was caused, explicit form of the error behaviour, and the consequence of the error. Method: Three human error classification criteria was chosen to classify human errors in major industrial accidents in chemical facilities: active vs. latent errors, external (behavior-based) classification, and internal (information processing-based) classification. Major industrial accidents which occurred in chemical facilities in Korea from 1997 to 2011 were analysed. Results: A total of 177 human errors were identified from 85 accident cases, and classified using the three criteria. Conclusion: Change in the number of human errors and frequencies of related facilities and industries were analysed. Application: The results provide insight on the pattern of human errors related to major industrial accidents in chemical facilities. In addition, they suggest that the accident investigation protocol is need to be improved.

Reactivation of fear memory renders consolidated amygdala synapses labile.

Kim, Jeongyeon,Song, Beomjong,Hong, Ingie,Kim, Jihye,Lee, Junuk,Park, Sungmo,Yong Eom, Jae,Lee, C Justin,Lee, Sukwon,Choi, Sukwoo The Society 2010 The Journal of neuroscience Vol.30 No.28

<P>It is believed that memory reactivation transiently renders consolidated memory labile and that this labile or deconsolidated memory is reconsolidated in a protein synthesis-dependent manner. The synaptic correlate of memory deconsolidation upon reactivation, however, has not been fully characterized. Here, we show that 3,5-dihydroxyphenylglycine (DHPG), an agonist for group I metabotropic glutamate receptors (mGluRI), induces synaptic depotentiation only at thalamic input synapses onto the lateral amygdala (T-LA synapses) where synaptic potentiation is consolidated, but not at synapses where synaptic potentiation is not consolidated. Using this mGluRI-induced synaptic depotentiation (mGluRI-depotentiation) as a marker of consolidated synapses, we found that mGluRI-depotentiation correlated well with the state of memory deconsolidation and reconsolidation in a predictable manner. DHPG failed to induce mGluRI-depotentiation in slices prepared immediately after reactivation when the reactivated memory was deconsolidated. DHPG induced mGluRI-depotentiation 1 h after reactivation when the reactivated memory was reconsolidated, but it failed to do so when reconsolidation was blocked by a protein synthesis inhibitor. To test the memory-specificity of mGluRI-depotentiation, conditioned fear was acquired twice using two discriminative tones (2.8 and 20 kHz). Under this condition, mGluRI-depotentiation was fully impaired in slices prepared immediately after reactivation with both tones, whereas mGluRI-depotentiation was partially impaired immediately after reactivation with the 20 kHz tone. Consistently, microinjection of DHPG into the LA 1 h after reactivation reduced fear memory retention, whereas DHPG injection immediately after reactivation failed to do so. Our findings suggest that, upon memory reactivation, consolidated T-LA synapses enter a temporary labile state, displaying insensitivity to mGluRI-depotentiation.</P>

복합화력발전소 경영진의 안전관심이 직원의 안전참여에 미치는 영향관계에서 조직요인의 매개효과 분석

최재우(JaeWoo Choi),엄성인(SungIn Um),홍인기(InGi Hong) 한국가스학회 2016 한국가스학회지 Vol.20 No.3

조직특성 및 안전문화는 매우 다양한 요인들을 포함하고 있으며, 그러한 안전문화의 향상을 위해서는 다양한 방법으로 접근되어야 한다. 구조방정식모형 분석을 통해 복합화력발전소의 안전문화 요인의 영향관계 검증결과 경영진의 관심도가 증가할수록 교육훈련정도의 향상과, 의사소통 및 안전참여의 향상에 긍정적인 역할을 함을 알 수 있었다. 그리고, 교육훈련 강도가 높을수록 근무향상에 도움이 될 것이 예측되었다. Organization characteristics and safety culture contains a wide variety of factors. It should be accessed in a variety of ways in order to improve such a safety culture. Thru by analyzing the safety culture factor of combined-cycle-power plants, it was found to be a positive role in the improvement and enhancement for the improving of safety training, communication and training participation level by structural equation modeling analysis as the management’s interest is increased. As the safety training is emphasized, it would be help to improve work participation.

Large-scale analysis of posttranslational modifications in the hippocampus of patients with Alzheimer's disease using pI shift and label-free quantification without enrichment.

Kang, Taewook,Kim, Jae Ho,Hong, Ingie,Park, Nam Hyun,Park, Nanhyun,Heinsen, Helmut,Lee, Joo-Yong,Ravid, Rivka,Ferrer, Isidro,Yoo, Jong Shin,Kwon, Kyung-Hoon,Park, Young Mok Springer-Verlag 2014 Analytical and Bioanalytical Chemistry Vol.406 No.22

<P>Posttranslational modifications modulate protein function in cells. Global analysis of multiple posttranslational modifications can provide insight into physiology and disease, but presents formidable challenges. In the present study, we used a technique that does not require target enrichment to analyze alterations in the phosphorylation and ubiquitination of proteins from patients with Alzheimer's disease (AD). Guided by our previous findings, we applied three strategies to further our understanding of the dysregulation of posttranslationally modified proteins. We first identified phosphorylation sites by determining peptide pI shifts using OFFGEL. Second, using tandem mass spectrometry, we determined the ubiquitination status of the proteins using an assay for a trypsin digestion remnant of ubiquitination (Gly-Gly). Third, for large-scale discovery, we quantified the global differences in protein expression. Of the proteins expressed in AD tissue at levels of 2.0 or greater compared with controls, 60 were phosphorylated and 56 were ubiquitinated. Of the proteins expressed at levels of 0.5 or lower compared with controls, 81 were phosphorylated and 56 were ubiquitinated. Approximately 98?% of the phosphopeptides exhibited a pI shift. We identified 112 new phosphorylation sites (51.38?%), and 92 new ubiquitination sites (96.84?%). Taken together, our findings suggest that analysis of the alterations in posttranslationally modified proteins may contribute to understanding the pathogenesis of AD and other diseases.</P>