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Nature Cancer 2024年第3期5卷 400-419页

作者： Huang, Yu-Kai Cheng, Wei-Chung Kuo, Ting-Ting Yang, Juan-Cheng Wu, Yang-Chang Wu, Heng-Hsiung Lo, Chia-Chien Hsieh, Chih-Ying Wong, Sze-Ching Lu, Chih-Hao Wu, Wan-Ling Liu, Shih-Jen Li, Yi-Chuan Lin, Ching-Chan Shen, Chia-Ning Hung, Mien-Chie Lin, Jaw-Town Yeh, Chun-Chieh Sher, Yuh-Pyng Graduate Institute of Biomedical Sciences China Medical University Taichung Taiwan Cancer Biology and Precision Therapeutics Center China Medical University Taichung Taiwan Ph.D. Program for Cancer Biology and Drug Discovery China Medical University and Academia Sinica Taichung Taiwan School of Chinese Medicine College of Chinese Medicine China Medical University Taichung Taiwan Graduate Institute of Integrated Medicine College of Chinese Medicine China Medical University Taichung Taiwan Department of Medical Laboratory Science and Biotechnology College of Medical and Health Science Asia University Taichung Taiwan Center for Molecular Medicine China Medical University Hospital Taichung Taiwan Institute of Bioinformatics and Systems Biology National Yang Ming Chiao Tung University Taipei Taiwan National Institute of Infectious Diseases and Vaccinology National Health Research Institutes Miaoli Taiwan Graduate Institute of Medicine College of Medicine Kaohsiung Medical University Kaohsiung Taiwan Department of Biological Science and Technology China Medical University Taichung Taiwan Division of Hematology and Oncology China Medical University Hospital Taichung Taiwan Genomics Research Center Academia Sinica Taipei Taiwan Division of Gastroenterology and Hepatology Department of Internal Medicine E-Da Hospital Kaohsiung Taiwan Department of Medicine School of Medicine China Medical University Taichung Taiwan Department of Surgery Organ Transplantation Center China Medical University Hospital Taichung Taiwan Institute of Biochemistry and Molecular Biology China Medical University Taichung Taiwan

Kirsten rat sarcoma virus (KRAS) signaling drives pancreatic ductal adenocarcinoma (PdAC) malignancy, which is an unmet clinical need. Here, we identify a disintegrin and metalloproteinase domain (AdAM)9 as a modulator of PdAC progression via stabilization of wild-type and mutant KRAS proteins. Mechanistically, AdAM9 loss increases the interaction of KRAS with plasminogen activator inhibitor 1 (PAI-1), which functions as a selective autophagy receptor in conjunction with light chain 3 (LC3), triggering lysosomal degradation of KRAS. Suppression of AdAM9 by a small-molecule inhibitor restricts disease progression in spontaneous models, and combination with gemcitabine elicits dramatic regression of patient-derived tumors. Our findings provide a promising strategy to target the KRAS signaling cascade and demonstrate a potential modality to enhance sensitivity to chemotherapy in PdAC. © The Author(s), under exclusive licence to Springer Nature America, Inc. 2024.

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Jing-Si Herbal Tea Suppresses H2O2-Instigated Inflammation and Apoptosis by Inhibiting Bax and Mitochondrial Cytochrome C Release in HIG-82 Synoviocytes

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Environmental Toxicology 2024年第12期39卷 5347-5356页

作者： Kao, Shih-Wen Chang, Yu-Chun Lin, Feng-Huei Huang, Tai-Lung Chen, Tung-Sheng Lin, Shinn-Zong Lin, Kuan-Ho Kuo, Wei-Wen Ho, Tsung-Jung Huang, Chih-Yang Graduate Institute of Aging Medicine China Medical University Taichung Taiwan Department of Orthopedic Surgery Chung-Shan Medical University Hospital Taichung Taiwan Department of Biological Science and Technology College of Life Sciences China Medical University Taichung Taiwan Cardiovascular and Mitochondrial Related Disease Research Center Hualien Tzu Chi Hospital Buddhist Tzu Chi Medical Foundation Hualien Taiwan Institute of Biomedical Engineering College of Medicine and College of Engineering National Taiwan University Taipei Taiwan Division of Biomedical Engineering and Nanomedicine Research National Health Research Institute Miaoli Taiwan Department of Orthopedics Chung-Kang Branch Cheng Ching General Hospital Taichung Taiwan School of Life Science National Taiwan Normal University Taipei Taiwan Department of Neurosurgery Hualien Tzu Chi Hospital Buddhist Tzu Chi Medical Foundation Hualien Taiwan Bioinnovation Center Buddhist Tzu Chi Medical Foundation Hualien Taiwan Department of Emergency Medicine China Medical University Hospital Taichung Taiwan College of Medicine China Medical University Taichung Taiwan Ph.D. Program for Biotechnology Industry China Medical University Taichung Taiwan School of Pharmacy China Medical University Taichung Taiwan School of Post-Baccalaureate Chinese Medicine College of Medicine Tzu chi University Hualien Taiwan Department of Chinese Medicine Hualien Tzu Chi Hospital Buddhist Tzu Chi Medical Foundation Tzu Chi University Hualien Taiwan Integration Center of Traditional Chinese and Modern Medicine Hualien Tzu Chi Hospital Buddhist Tzu Chi Medical Foundation Hualien Taiwan Graduate Institute of Biomedical Sciences China Medical University Taichung Taiwan Department of Medical Laboratory Science and Biotechnology Asia University Taichung Taiwan

Inflammation is an intrinsic protective mechanism against various forms of cellular injuries in humans;however, its undesired activation results in tissue damage and cell death. The onset of chronic inflammation and oxidative stress are the key characteristics of autoimmune inflammatory diseases such as rheumatoid arthritis (RA), for which an effective treatment is yet to be developed. Therefore, in this study, we investigated the protective effects and molecular mechanisms of a novel herbal preparation, Jing-Si herbal tea (JS), against H2O2-induced inflammation and cellular damage in HIG-82 synoviocytes. We found that JS did not show any significant alterations in cell viability at 2O2-induced pathological oxidative stress (ROS) in HIG-82 cells. Interestingly, JS treatment not only reduced the ROS levels but also significantly repressed the protein expressions of collagen degrading proteases in a dose-dependent manner. Treatment with JS showed enhanced cell viability against H2O2-induced toxic ROS levels. The expressions of cell protective aggrecan, Collagen II, and Bcl-2 were increased, whereas MMP-13, AdAMTS-2, Cytochrome C, and cleaved Caspase 3 were decreased by JS under inflammatory agents H2O2, MIA, LPS, and TNF-α treatment, respectively, in HIG-82 cells. Interestingly, the cytoprotective effect of JS treatment was attributed to a decreased mitochondrial localization of Bax and a reduction of Cytochrome C release into the cytoplasm of H2O2-treated HIG-82 cells. Collectively, our results suggest a novel protective mechanism of JS for RA treatment, which could be potentially applied as a complementary treatment or as an alternative therapeutic approach to mitigate inflammatory diseases. © 2024 Wiley Periodicals LLC.

关键词： Cell death

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Ecological Risk Assessment and Corrective Actions of dioxins Polluted Sediment in the Brine Water Storage Pond of Chemical Plant

SSRN

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SSRN 2022年

作者： Huang, Wen-Yen Huang, Chi-Wei Lin, Chitsan Li, Yi-Lin Huang, Tsung-Po Bui, Xuan-Thanh Ngo, Huu Hao Department of Marine Environmental Engineering National Kaohsiung University of Science and Technology Kaohsiung81157 Taiwan Ph.D. Program in Maritime Science and Technology College of Maritime National Kaohsiung University of Science and Technology Kaohsiung81157 Taiwan 268 Ly Thuong Kiet Street District 10 Ho Chi Minh City700000 Viet Nam Linh Trung Ward Ho Chi Minh City700000 Viet Nam School of Civil and Environmental Engineering University of Technology Sydney SydneyNSW2007 Australia

despite the high toxicity of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCdd/Fs, or dioxins), the case studies about PCdd/Fs contamination in sediment are still few and its ecological impacts are not fully elucidated. To improve the risk management of PCdd/Fs pollution in sediment, the present study conducted the environmental risk assessment of the brine water storage pond near a chemical plant with high PCdd/Fs pollution potential before and after corrective actions. The results showed the PCdd/Fs accumulation in the fish and crab from the brine water storage pond, and the PCdd/Fs concentrations in biota were all higher than the food safety standard in Taiwan (3.5 pg-TEQ/g). Furthermore, the different indexes showed high degree of pollution including contamination factor (CF), modified degree of contamination (mCd), and pollution index (PI) in the PCdd/Fs polluted sediment. High biological risk indexes such as potential ecological risk index (RI) and risk quotient (RQ) were also observed in the PCdd/Fs contaminated sediment before the corrective actions. After the corrective actions such as institutional/engineering control and remediation, the CF, mCd, and PI decreased by 20–41%. The RI and RQ were also decreased by 41–56%. In conclusion, the corrective actions applied in the present study could help decrease the pollution and ecological risk of PCdd/Fs in the polluted sediment of the study site, which might further decrease the environmental risk to an acceptable level for the stakeholders if keeping implementation of the corrective actions. © 2022, The Authors. All rights reserved.

关键词： Risk management

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Oxidation Behaviour of Al2O3-Forming Cr-Based Alloys at Elevated Temperatures

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SSRN 2023年

作者： Liu, Che-Jen Huang, Kai-Yu Lin, Wei-Chih Lo, Kai-Chi Hsu, Wei-Lin Gorsse, Stéphane Yeh, An-Chou Ph.D. Program in Prospective Functional Materials Industry National Tsing Hua University 101 Sec. 2 Kuang-Fu Road Hsinchu30013 Taiwan High Entropy Materials Center National Tsing Hua University 101 Sec. 2 Kuang-Fu Road Hsinchu30013 Taiwan Department of Materials Science and Engineering National Tsing Hua University 101 Sec. 2 Kuang-Fu Road Hsinchu30013 Taiwan University of Bordeaux CNRS Bordeaux INP ICMCB UMR 5026 PessacF-33600 France

This research focused on oxidation behaviours of Al-bearing Cr-based alloys at 1100-1400 ˚C for up to 24 hours. Experimental observations indicate that Al2O3 protective oxide formed mainly on the matrix BCC phase, and complex oxides formation occurred in the vicinity of C14 Laves phase, such as Cr2O3, AlTaO4, CrTaO4, and Ta2O5, leading to some internal Al2O3 and AlN formation. Although the increase in Al content could promote the formation of protective Al2O3, it also caused oxide spallation due to CTE mismatch. This study may provide some insights in the development of future oxidation-resistant Cr-based alloy compositions. © 2023, The Authors. All rights reserved.

关键词： Aluminum oxide

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Enhanced electrochemical detection of tartrazine in beverages and liquid soap via nickel phosph.d.-adorned functionalized carbon nanofibers

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Journal of the Taiwan Institute of Chemical Engineers 2024年 157卷

作者： Gokulkumar, Kumar Huang, Song-Jeng Kogularasu, Sakthivel Aljuwayid, Ahmed M. Maheshwaran, Selvarasu Govindasamy, Mani Department of Mechanical Engineering National Taiwan University of Science and Technology Taipei City106335 Taiwan Super micro mass research and technology center Cheng Shiu University Kaohsiung833301 Taiwan Center for Environmental Toxin and Emerging-Contaminant Research Cheng Shiu University Kaohsiung833301 Taiwan Department of Chemistry College of Science King Saud University P. O. Box 2455 Riyadh11451 Saudi Arabia Department of Aeronautics and Astronautics National Cheng Kung University Tainan701 Taiwan International Ph.D. Program In Innovative Technology of Biomedical Engineering and Medical Devices Ming Chi University of Technology New Taipei City243303 Taiwan Tamil Nadu Chennai602105 India

Background: Tartrazine (TAT) is a widely used food colorant dye, offering an orange-yellow hue in various products such as foods, cosmetics, and pharmaceuticals. despite its popularity, TAT is banned in several countries due to its potential health risks, including respiratory issues, migraines, and skin allergies. Moreover, TAT is linked with adverse effects on human physiology, including mutagenicity, biliary cirrhosis, changes in liver and kidney functions, and neurodegeneration at varying doses. Consequently, the detection of this food additive is crucial for safeguarding human health and protecting aquatic organisms. Methods: In this study, a novel sensor was developed for the detection of TAT, utilizing a composite material made from nickel phosph.d. decorated with functionalized carbon nanofiber (Ni2P@f-CNF). The Ni2P@f-CNF was synthesized and characterized through several techniques, including X-ray diffraction, X-ray photoelectron spectroscopy, field emission-scanning electron microscopy, and elemental mapping. The composite was then integrated with a glassy carbon electrode to create a sensor. The sensor's performance was evaluated in terms of detection limit, linear range, selectivity, sensitivity, reproducibility, repeatability, and long-term stability. Main Findings: The developed Ni2P@f-CNF composite sensor displayed a lower detection limit of 0.011 µM and a broad linear range from 0.01 to 1875 µM. Its selectivity and sensitivity were exceptional, primarily due to the catalytic activity of the Ni2P@f-CNF composite towards TAT. The sensor also demonstrated excellent reproducibility, repeatability, and notable long-term stability. Importantly, when applied in real-world scenarios, the sensor successfully detected TAT in soft drink and liquid soap samples, yielding high recovery rates between 97.45 % to 99.37 % and 98.26 % to 99.01 %, respectively, underscoring its potential applicability in practical settings. © 2024 Taiwan Institute of Chemical Engineer

关键词： Nickel compounds

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Assessment of sources and health risks of heavy metals in metropolitan household dust among preschool children: The LEAPP-HIT study

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Journal of Environmental Management 2024年 352卷 120015页

作者： Kao, Chi-Sian Wang, Ying-Lin Jiang, Chuen-Bin Tai, Pei-Ju Chen, Yi-Hua Chao, Hsing-Jasmine Lo, Yu-Chun Hseu, Zeng-Yei Hsi, Hsing-Cheng Chien, Ling-Chu School of Public Health College of Public Health Taipei Medical University Taipei Taiwan Graduate Institute of Environmental Engineering National Taiwan University Taipei Taiwan Department of Pediatric Gastroenterology Hepatology and Nutrition MacKay Children's Hospital Taipei Taiwan Department of Medicine MacKay Medical College SanZhi District New Taipei City Taiwan Neuroscience Research Center Taipei Medical University Taipei Taiwan Ph.D. Program in Medical Neuroscience College of Medical Science and Technology Taipei Medical University Taipei Taiwan Department of Agricultural Chemistry National Taiwan University Taipei Taiwan Nutrition Research Center Taipei Medical University Hospital Taipei Taiwan

The most common construction material used in Taiwan is concrete, potentially contaminated by geologic heavy metals (HMs). Younger children spend much time indoors, increasing HM exposure risks from household dust owing to their behaviors. We evaluated arsenic (As), cadmium (Cd), and lead (Pb) concentrations in fingernails among 280 preschoolers between 2017 and 2023. We also analyzed HM concentrations, including As, Cd, Pb, chromium (Cr), nickel (Ni), copper (Cu), zinc (Zn), iron (Fe), and manganese (Mn), in 90 household dust and 50 road dust samples from a residential area where children lived between 2019 and 2021 to deepen the understanding of sources and health risks of exposure to HMs from household dust. The average As, Cd, and Pb concentrations in fingernails were 0.12 ± 0.06, 0.05 ± 0.05, and 0.95 ± 0.77 μg/g, respectively. Soil parent materials, indoor construction activities, vehicle emissions, and mixed indoor combustion were the pollution sources of HMs in household dust. Higher Cr and Pb levels in household dust may pose non-carcinogenic risks to preschoolers. Addressing indoor construction and soil parent materials sources is vital for children's health. The finding of the present survey can be used for indoor environmental management to reduce the risks of HM exposure and avoid potential adverse health effects for younger children. © 2024 Elsevier Ltd

关键词： Heavy metals

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Ultrasound-guided drug delivery system utilizing piezocatalytic MoS2 nanomaterials for anti-inflammatory therapy

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Nano Energy 2024年 127卷

作者： Lin, Ssu-Chi Joshi, Ravindra Ganguly, Anindita Barman, Snigdha Roy Pal, Arnab Kaswan, Kuldeep Liu, Kuei-Lin Nain, Amit Kao, Fu-Cheng Lin, Zong-Hong Department of Biomedical Engineering National Taiwan University Taipei10167 Taiwan Institute of Biomedical Engineering National Tsing Hua University Hsinchu30013 Taiwan Department of Power Mechanical Engineering National Tsing Hua University Hsinchu30013 Taiwan Internet of Senses Research Center National Tsing Hua University Hsinchu30013 Taiwan International Intercollegiate Ph.D. Program National Tsing Hua University Hsinchu30013 Taiwan Department of Materials Engineering Indian Institute of Science Karnataka Bangalore560012 India Department of Orthopaedic Surgery Chang Gung Memorial Hospital Taoyuan33305 Taiwan College of Medicine Chang Gung University Taoyuan33302 Taiwan

Traditional drug delivery systems lack the potential of controlled drug release, thereby decreasing drug utilization and release efficiency. Herein, a next generation of stimuli-responsive drug delivery platform is designed based on piezocatalytic molybdenum disulfide nanoflowers (MoS2 NFs) which can be triggered by ultrasound (US) stimulation for effective acute inflammation therapy. Under US irradiation, MoS2 NFs undergoes piezocatalysis to generate reactive oxygen species (ROS) owing to piezoelectric polarization, thus releasing loaded anti-inflammatory drug Indomethacin (INd) to the targeted inflammation site. The cumulative release of INd elevated significantly with the increase in the duration for US exposure due to the amplified ROS generation, which displayed a highly controllable nature of the as-designed drug delivery platform. For convenient applications, the INd loaded MoS2 NFs (INd@MoS2 NFs) was functionalized onto commercial dressings and their tunable in-vivo drug release performance was demonstrated in paw edema model. INd@MoS2 NFs upon US irradiation, controllably released INd into the site-specific inflamed paw which significantly inhibited 56 % of paw swelling in 6 h by suppressing the infiltration of neutrophils and expression of pro-inflammatory cytokines such as tumor necrosis factor-α (TNF-α). The highly controllable drug delivery system holds great potential in facilitating personalized, user-friendly theranostic applications with improved patient outcomes. © 2024 Elsevier Ltd

关键词： Ultrasonics

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The role of input imaging combination and AdC threshold on segmentation of acute ischemic stroke lesion using U-Net

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European Radiology 2023年第9期33卷 6157-6167页

作者： Li, Ya-Hui Lin, Shao-Chieh Chung, Hsiao-Wen Chang, Chia-Ching Peng, Hsu-Hsia Huang, Teng-Yi Shen, Wu-Chung Tsai, Chon-Haw Lo, Yu-Chien Lee, Tung-Yang Juan, Cheng-Hsuan Juan, Cheng-En Chang, Hing-Chiu Liu, Yi-Jui Juan, Chun-Jung Graduate Institute of Biomedical Electronics and Bioinformatics National Taiwan University Taipei Taiwan Department of Medical Imaging China Medical University Hsinchu Hospital No. 199 Sec. 1 Xinglong Rd. Zhubei City Hsinchu County 302 Hsinchu Taiwan Ph.D. Program in Electrical and Communication Engineering Feng Chia University Taichung Taiwan Department of Electrical Engineering National Taiwan University Taipei Taiwan Department of Management Science National Yang Ming Chiao Tung University Hsinchu Taiwan Department of Biomedical Engineering and Environmental Sciences National Tsing Hua University Hsinchu Taiwan Department of Electrical Engineering National Taiwan University of Science and Technology Taipei Taiwan Department of Radiology School of Medicine College of Medicine China Medical University Taichung Taiwan Department of Medical Imaging Medical University Hospital Taichung Taiwan Department of Neurology China Medical University Hospital Taichung Taiwan Cheng Ching Hospital Taichung Taiwan Master’s Program of Biomedical Informatics and Biomedical Engineering Feng Chia University Taichung Taiwan Department of Automatic Control Engineering Feng Chia University No. 100 Wenhwa Rd. Seatwen Taichung 40724 Taiwan Department of Biomedical Engineering The Chinese University of Hong Kong ERB1112 11/F William M.W. Mong Engineering Building N.T Shatin Hong Kong Multi-Scale Medical Robotics Center The Chinese University of Hong Kong N.T Shatin Hong Kong Department of Biomedical Engineering National Defense Medical Center Taipei Taiwan Department of Computer Science and Information Engineering National Taiwan University Taipei Taiwan

Background: To evaluate the effect of the weighting of input imaging combo and AdC threshold on the performance of the U-Net and to find an optimized input imaging combo and AdC threshold in segmenting acute ischemic stroke (AIS) lesion. Methods: This study retrospectively enrolled a total of 212 patients having AIS. Four combos, including AdC-AdC-AdC (AAA), dWI-AdC-AdC (dAA), dWI-dWI-AdC (ddA), and dWI-dWI-dWI (ddd), were used as input images, respectively. Three AdC thresholds including 0.6, 0.8 and 1.8 × 10^–3 mm²/s were applied. dice similarity coefficient (dSC) was used to evaluate the segmentation performance of U-Nets. Nonparametric Kruskal–Wallis test with Tukey–Kramer post-hoc tests were used for comparison. A p <.05 was considered statistically significant. Results: The dSC significantly varied among different combos of images and different AdC thresholds. Hybrid U-Nets outperformed uniform U-Nets at AdC thresholds of 0.6 × 10^–3 mm²/s and 0.8 × 10^–3 mm²/s (p <.001). The U-Net with imaging combo of ddd had segmentation performance similar to hybrid U-Nets at an AdC threshold of 1.8 × 10^–3 mm²/s (p =.062 to 1). The U-Net using the imaging combo of dAA at the AdC threshold of 0.6 × 10^–3 mm²/s achieved the highest dSC in the segmentation of AIS lesion. Conclusions: The segmentation performance of U-Net for AIS varies among the input imaging combos and AdC thresholds. The U-Net is optimized by choosing the imaging combo of dAA at an AdC threshold of 0.6 × 10^–3 mm²/s in segmentating AIS lesion with highest dSC. Key Points: • Segmentation performance of U-Net for AIS differs among input imaging combos. • Segmentation performance of U-Net for AIS differs among AdC thresholds. • U-Net is optimized using dAA with AdC = 0.6 × 10^–3mm²/s. © 2023, The Author(s), under exclusive licence to European Society of Radiology.

关键词： deep Learning diffusion Magnetic Resonance Imaging Ischemic Stroke Neural Networks, computer Retrospective Study

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PVA-based bioinks for 3d bioprinting: A comprehensive review of their applications in tissue engineering

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Bioprinting 2025年 49卷

作者： Johari, Narges Adabavazeh, Zary Baino, Francesco Materials Engineering Group Golpayegan College of Engineering Isfahan University of Technology Golpayegan Iran Ph.D. Program Graduate Institute of Precision Manufacturing National Chin-Yi University of Technology Taichung Taiwan Institute of Materials Physics and Engineering Department of Applied Science and Technology Politecnico di Torino Torino Italy

3d bioprinting is an innovative approach that overcomes the limitations of traditional methods for creating cell-laden biomaterials and constructs. It allows for the fabrication of complex and biologically active tissue structures. This review aims to provide a comprehensive evaluation of polyvinyl alcohol (PVA)-based bioinks within a 3d bioprinting framework. PVA-based bioinks exhibit remarkable properties, such as biocompatibility, biodegradability, and the ability to enhance cell growth and differentiation. These properties make them appropriate for many tissue engineering applications. The study evaluates the physicochemical and biological properties of PVA bioinks, including how they combine with other materials such as gelatin, chitin, chitosan, alginate, agarose, cellulose, κ-carrageenan, methacrylate, nanoparticles, mineral additives, carbon nanotubes, graphene oxide, and extracellular matrix components. Furthermore, this review evaluates the benefits of market availability and enhanced printing resolution, in addition to the challenges posed by complexity, dependency on support baths, and the risk of contamination. The objective of this review is to draw attention to the capabilities of PVA-based bioinks and provide guidelines for future research to improve the effectiveness of these materials in tissue engineering and regenerative medicine. © 2025 The Authors

关键词： Bioink Bioprinting Polyvinyl alcohol PVA-based bioinks

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Explaining heterogeneity in medial entorhinal cortex with task-driven neural networks 21

Explaining heterogeneity in medial entorhinal cortex with ta...

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Proceedings of the 35th International Conference on Neural Information Processing Systems

作者： Aran Nayebi Alexander Attinger Malcolm G. Campbell Kiah Hardcastle Isabel I.C. Low Caitlin S. Mallory Gabriel C. Mel Ben Sorscher Alex H. Williams Surya Ganguli Lisa M. Giocomo daniel L.K. Yamins Neurosciences Ph.D. Program Stanford University Department of Neurobiology Stanford University Neurosciences Ph.D. Program Stanford University and Department of Neurobiology Stanford University and Wu Tsai Neurosciences Institute Stanford University Department of Applied Physics Stanford University Department of Statistics Stanford University and Wu Tsai Neurosciences Institute Stanford University Department of Applied Physics Stanford University and Wu Tsai Neurosciences Institute Stanford University and Facebook AI Research Facebook Inc. Department of Neurobiology Stanford University and Wu Tsai Neurosciences Institute Stanford University Department of Computer Science Stanford University and Department of Psychology Stanford University and Wu Tsai Neurosciences Institute Stanford University

ISBN: (纸本)9781713845393

Medial entorhinal cortex (MEC) supports a wide range of navigational and memory related behaviors. Well-known experimental results have revealed specialized cell types in MEC — e.g. grid, border, and head-direction cells — whose highly stereotypical response profiles are suggestive of the role they might play in supporting MEC functionality. However, the majority of MEC neurons do not exhibit stereotypical firing patterns. How should the response profiles of these more "heterogeneous" cells be described, and how do they contribute to behavior? In this work, we took a computational approach to addressing these questions. We first performed a statistical analysis that shows that heterogeneous MEC cells are just as reliable in their response patterns as the more stereotypical cell types, suggesting that they have a coherent functional role. Next, we evaluated a spectrum of candidate models in terms of their ability to describe the response profiles of both stereotypical and heterogeneous MEC cells. We found that recently developed task-optimized neural network models are substantially better than traditional grid cell-centric models at matching most MEC neuronal response profiles — including those of grid cells themselves — despite not being explicitly trained for this purpose. Specific choices of network architecture (such as gated nonlinearities and an explicit intermediate place cell representation) have an important effect on the ability of the model to generalize to novel scenarios, with the best of these models closely approaching the noise ceiling of the data itself. We then performed in silico experiments on this model to address questions involving the relative functional relevance of various cell types, finding that heterogeneous cells are likely to be just as involved in downstream functional outcomes (such as path integration) as grid and border cells. Finally, inspired by recent data showing that, going beyond their spatial response selectivity, MEC cells

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