700 research outputs found
Posterior parietal cortex mediates fear renewal in a novel context
No full textThe return of fear following extinction therapy is an important issue associated with the treatment of many fear-related disorders. Fear renewal is a suitable model, with which context-dependent modulation of the fear response can be examined. In this model, any context outside of an extinction context (e.g., novel or familiar contexts) could evoke relapse of the fear response. However, brain regions associated with context-dependent modulation are not fully understood. The posterior parietal cortex (PPC) is considered a center for integrating multisensory information and making decisions. To study its role in the contextual modulation of fear relapse, we reversibly inactivated the PPC in mice before they were exposed to various contexts after extinction training. When muscimol was infused into the PPC, fear renewal was impaired in a novel context, but not in a familiar context. Fear relapses were blocked during optogenetic inhibition of the PPC, only when animals were placed in a novel context. We propose that the neural activity of the PPC is necessary for the relapse of a precise response to an extinguished conditioned stimulus in a novel context. © 2020 The Author(s).1
맥락 변화에 따른 공포 기억을 조절하는 후두정피질-전측대상회피질 회로 연구
No full textPosterior parietal cortex;anterior cingulate cortex;fear renewal;context;parvalbumin neuron;post-traumatic stress disorderThe ability to process contextual stimuli for rapid adaptation to novel circumstances is funda- mental for survival. However, maladaptive information processing can lead to various fear-related disorders. While previous studies have emphasized the importance of cortical pathways in context- dependent fear responses, the precise relationship between novel contextual stimuli and fear reac- tions within cortical networks remains incompletely understood. In this study, I demonstrated that neural activity in the posterior parietal cortex (PPC) plays a crucial role in the relapse of conditioned fear responses to an extinguished stimulus in a novel context. Fear relapses were blocked when the PPC was inhibited, particularly in a novel context, but not in a familiar context. Next, I identified the functional output region of the PPC, revealing that the connection between the PPC and the anterior cingulate cortex (ACC) regulates extinguished fear responses in a novel context. Enhanced calcium activity was observed in ACC neurons receiving PPC projections (PPC-ACC) during fear renewal in a novel context, and increased synaptic activity was examined in PPC-ACC neurons projecting to the basolateral amygdala (BLA) upon fear renewal in a novel context. Moreover, PPC neurons projecting to parvalbumin (PV)-expressing interneurons in the ACC (PPC-ACCPV) con- trolled the relapse of fear memory in a novel context. Furthermore, chronic fluoxetine administra- tions, used in treating fear-related disorders including post-traumatic stress disorders, successfully blocked optogenetically induced high levels of fear response in PPC-ACCPV neurons. In summary, this study deepens our understanding of the neural mechanisms within the PPC-ACC pathway that modulate fear memory relapse in a novel context, contributing to the broader knowledge of fear memory regulation and its implications for managing fear-related disorders. Keywords: Posterior parietal cortex, anterior cingulate cortex, fear renewal, context, parvalbumin neuron, post-traumatic stress disorder|맥락 정보를 처리하여 새로운 환경에 빠르게 적응하는 능력은 생존에 필수적이다. 하지만 정보 처리가 잘 이루어지지 않으면 공포와 관련된 다양한 질병을 유발할 수 있다. 이전 연구에서는 맥락 의존적인 공포반응이 일어날 때 대뇌피질 회로의 중요성이 강조되어왔으나, 피질 네트워크 안에서 새로운 맥락 정보와 공포 행동 사이의 정확한 관계는 아직 완전히 밝혀지지 않았다. 본 연구에서는, 후두정피질의 신경 활성이 새로운 환경에서 어떻게 소거된 자극이 조건화된 공포반응을 재발을 매개하는지 밝히고자 한다. 후두정피질을 억제하면 새로운 환경에서의 공포 재발이 차단되었으나, 익숙한 환경에서의 공포재발에는 영향을 미치지 않았다. 또한 후두정피질의 기능적인 출력 영역을 찾아내어 후두정피질과 전측대상회피질 간의 연결이 새로운 환경에서 소거되었던 공포 반응을 조절한다는 것을 밝혔다. 새로운 환경에서 공포 재발 시 후두정피질과 연결된 전측대상회피질 뉴런의 칼슘 신호가 증가하였고, 후두정피질-전측대상회피질 뉴런과 편도체로 신호를 보내는 전측대상회피질 뉴런사이의 시냅스 활성도 새로운 환경에서 공포재발 후 높아졌다. 더불어, 후두정피질의 신호를 받는 전측대상회피질 뉴런 중 파브알부민을 발현하는 억제성 뉴런이 새로운 환경에서의 공포기억 재발을 매개한다는 것을 밝혔다. 더욱이, 외상 후 스트레스 장애를 비롯한 공포와 관련된 질병의 치료에 사용하는 플루옥세틴의 장기투여가 광유전학에 의해 유도된 증가된 공포 반응을 효과적으로 약화시켰다. 요약하면, 본 연구는 후두정피질-전측대상회피질 회로가 새로운 환경에서 공포 기억 재발을 조절하는 신경 매커니즘을 규명함으로써, 공포 기억의 조절과 이와 관련된 병리적 현상의 이해를 확장하는데 기여한다.
핵심어: 후두정피질, 전측대상회피질, 공포 재발, 맥락, 파브알부민 뉴런, 외상 후 스트레스 장애Ⅰ. Introduction 1
1.1 Background and significance 1
1.2 Posterior parietal cortex 2
1.3 Medial prefrontal cortex 4
1.4 Rationale 6
1.5 Research objectives and hypotheses 7
1.5.1 Primary Objective · 7
1.5.2 Investigating the role of the PPC in fear memory 8
1.5.3 Identifying the functional connectivity of the PPC 8
1.5.4 Understanding the neural mechanism of the PPC-ACC pathway 8
1.6 Conclusion 9
Ⅱ. Materials & Methods 10
2.1 Animals 10
2.2 Stereotaxic surgeries 10
2.3 Behavioral assays 11
2.3.1 Fear conditioning apparatus 11
2.3.2 Fear behavioral procedure 12
2.3.3 Open maze apparatus 12
2.3.4 Open field 13
2.3.5 Y-maze 13
2.3.6 Novel object recognition 13
2.4 Optogenetics 13
2.5 Drug treatment 14
2.5.1 Muscimol 14
2.5.2 Fluoxetine 14
2.6 Fiber photometry 14
2.7 Slice electrophysiology 15
2.8 Histology 16
2.9 Statistical analysis 17
Ⅲ. Results 21
3 Investigating the role of the PPC in fear memory 21
3.1 Validation of fear renewal model 21
3.2 Pharmacological inactivation of the PPC in various contextual situations 25
3.2.1 Fear renewal in a novel context (ABC renewal) 25
3.2.2 Fear renewal in a familiar context (ABA renewal) 29
3.2.3 Extinction retrieval 32
3.2.4 Fear reinstatement 35
3.2.5 Fear retrieval in a novel context 38
3.3 Optogenetic manipulation of the PPC in various contextual situations 41
3.3.1 ABC renewal 41
3.3.2 ABA renewal 45
3.3.3 Fear conditioning 48
3.3.4 Extinction 48
3.3.5 Extinction retrieval 52
3.3.6 Differential activation of PPC cells in response to behavioral contexts 55
4 Identifying the functional connectivity of the PPC 57
4.1 Parietal-frontal circuit on ABC renewal 57
4.2 Parallel pathways in context-dependent fear renewal 63
4.3 Physiological properties of ACC-projecting PPC neurons after behaviors 66
5 Understanding the neural mechanism of the PPC-ACC pathway 69
5.1 In vivo calcium dynamics of PPC-ACC neurons 69
5.2 Histology for PPC-ACC projection profile 72
5.3 PPC-driven synaptic activity in BLA-projecting ACC neurons 75
5.4 Optogenetic manipulation of PPC-ACC subpopulations 82
5.5 Attenuation of fear relapse by SSRI treatment 88
5.6 The impact of fluoxetine administration on general mouse behaviors 92
Ⅳ. Discussion 96
Discussion 96
Ⅴ. References 101
References 101
Abstracts in Korean 110DoctordCollectio
High throughput single-molecule technology
No full textGreen Open Access added to TU Delft Institutional Repository ‘You share, we take care!’ – Taverne project https://www.openaccess.nl/en/you-share-we-take-care Otherwise as indicated in the copyright section: the publisher is the copyright holder of this work and the author uses the Dutch legislation to make this work public.BN/Chirlmin Joo LabSports & GamesBN/Bionanoscienc
Leaders of the field: What does the future hold for single molecule technology?
No full textIn recent years, single molecule technology has experienced a rapid growth, with exciting developments in fundamental research and real-world applications. Detecting and studying biological phenomena on thesingle molecule level requires a unique synergy between researchers working on instrumentation, physics, and the life sciences. In the iScience special issue ‘‘Single Molecule Technology – From Biotechnology toBiomedical Applications’’, guest edited by Amit Meller and Chirlmin Joo (Figure 1), we are highlighting a variety of research on nanopore technology, single molecule fluorescence, and a selection of other ultra-sensitive detection methods. More content in the special issue can be found here: https://www.sciencedirect.com/journal/iscience/special-issue/10PGSBV55N0. The guest editors in this backstory share their thoughts on what is currently exciting in the field, and the advances they think will make an impact in the near future.BN/Chirlmin Joo La
A study of two wireless telecommunications companies' globalization strategies : an analysis of Vodafone's and NTT DoCoMo's foreign investments
No full textThesis (M.B.A.)--Massachusetts Institute of Technology, Sloan School of Management, 2003 [first author]; and, (S.M.)--Massachusetts Institute of Technology, Sloan School of Management, 2003 [second author].Includes bibliographical references (leaves 117-119).by Hyungchul Joo and Peter D. Honkanen.M.B.A.S.M
Paving the way to single-molecule protein sequencing
No full textProteins are major building blocks of life. The protein content of a cell and an organism provides key information for the understanding of biological processes and disease. Despite the importance of protein analysis, only a handful of techniques are available to determine protein sequences, and these methods face limitations, for example, requiring a sizable amount of sample. Single-molecule techniques would revolutionize proteomics research, providing ultimate sensitivity for the detection of low-abundance proteins and the realization of single-cell proteomics. In recent years, novel single-molecule protein sequencing schemes that use fluorescence, tunnelling currents and nanopores have been proposed. Here, we present a review of these approaches, together with the first experimental efforts towards their realization. We discuss their advantages and drawbacks, and present our perspective on the development of single-molecule protein sequencing techniques.Accepted Author ManuscriptBN/Chirlmin Joo LabBN/Cees Dekker La
Unraveling proteins at the single molecule level using nanopores
No full textThe function and phenotype of a cell is determined by a complex network of interactions between DNA, RNA, proteins and metabolites. Therefore, a comprehensive approach that integrates genomics, transcriptomics, proteomics, and metabolomics is necessary to achieve full understanding of biological processes and disease. Recent technological developments have mostly focused on the study of genomes. DNA sequencing has become fast, cheap, and ubiquitous. The study of other -omes, especially the proteome, remains expensive and time-consuming...BN/Chirlmin Joo La
Completing the canvas: advances and challenges for DNA-PAINT super-resolution imaging
No full textSingle-molecule localization microscopy (SMLM) is a potent tool to examine biological systems with unprecedented resolution, enabling the investigation of increasingly smaller structures. At the forefront of these developments is DNA-based point accumulation for imaging in nanoscale topography (DNA-PAINT), which exploits the stochastic and transient binding of fluorescently labeled DNA probes. In its early stages the implementation of DNA-PAINT was burdened by low-throughput, excessive acquisition time, and difficult integration with live-cell imaging. However, recent advances are addressing these challenges and expanding the range of applications of DNA-PAINT. We review the current state of the art of DNA-PAINT in light of these advances and contemplate what further developments remain indispensable to realize live-cell imaging.Accepted Author ManuscriptBN/Chirlmin Joo La
Strategic plan for the built environment
No full textprepared by: the Oregon Department of Environmental Quality, Materials Management Program ; authors: Amanda Ingmire and Sun Joo Kim.Title from PDF cover (viewed on February 25, 2022).This archived document is maintained by the State Library of Oregon as part of the Oregon Documents Depository Program. It is for informational purposes and may not be suitable for legal purposes.Includes bibliographical references (pages 46-48).Mode of access: Internet from the Oregon Government Publications Collection.Text in English
Small RNA-directed DNA elimination: the molecular mechanism and its potential for genome editing
No full textTransposable elements have both detrimental and beneficial effects on their host genome. Tetrahymena is a unicellular eukaryote that deals with transposable elements in a unique way. It has a separate somatic and germline genome in two nuclei in a single cell. During sexual reproduction, a small RNA directed system compares the germline and somatic genome to identify transposable elements and related sequences. These are subsequently marked by heterochromatin and excised. In this Review, current knowledge of this system and the gaps therein are discussed. Additionally, the possibility to exploit the Tetrahymena machinery for genome editing and its advantages over the widely used CRISPR-Cas9 system will be explored. While the bacterial derived CRISPR-Cas9 has difficulty to access eukaryotic chromatin, Tetrahymena proteins are adept at acting in a chromatin context. Furthermore, Tetrahymena based gene therapy in humans might be a safer alternative to Cas9 because the latter can trigger an immune response.BN/Chirlmin Joo La
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