31 results on '"Gschwind T"'
Search Results
2. Brain microglia in psychiatric disorders
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Mondelli, Valeria, Vernon, Anthony C, Turkheimer, Federico, Dazzan, Paola, Pariante, Carmine M, Frost, JL, Schafer, DP, Banati, RB, Newcombe, J, Gunn, RN, al., et, Tang, Y, Le, W, Estes, ML, McAllister, AK, Ransohoff, RM, Davalos, D, Grutzendler, J, Yang, G, Peferoen, LA, Vogel, DY, Ummenthum, K, Norden, DM, Trojanowski, PJ, Villanueva, E, Navarro, E, Godbout, JP, Kreisel, T, Frank, MG, Licht, T, Wachholz, S, Eßlinger, M, Plümper, J, Manitz, MP, Juckel, G, Friebe, A, Trépanier, MO, Hopperton, KE, Mizrahi, R, Mechawar, N, Bazinet, RP, Torres-Platas, SG, Cruceanu, C, Chen, GG, Turecki, G, Steiner, J, Bielau, H, Brisch, R, Schnieder, TP, Trencevska, I, Rosoklija, G, Fillman, SG, Cloonan, N, Catts, VS, Rupprecht, R, Papadopoulos, V, Rammes, G, Qiu, ZK, Li, MS, He, JL, Hannestad, J, Gallezot, JD, Schafbauer, T, Israel, I, Ohsiek, A, Al-Momani, E, Mirzaei, N, Tang, SP, Ashworth, S, Gulyás, B, Makkai, B, Kása, P, Turkheimer, FE, Rizzo, G, Bloomfield, PS, Owen, DR, Yeo, AJ, DellaGioia, N, Setiawan, E, Wilson, AA, Su, L, Faluyi, YO, Hong, YT, Haarman, BC, Lek, RF Riemersma-Van der, Groot, JC de, Berckel, BN van, Bossong, MG, Boellaard, R, Doorduin, J, Vries, EF de, Willemsen, AT, Dierckx, RA, Klein, HC, Takano, A, Arakawa, R, Ito, H, Kenk, M, Selvanathan, T, Rao, N, Selvaraj, S, Veronese, M, Coughlin, JM, Wang, Y, Ambinder, EB, Doef, TF van der, Witte, LD de, Sutterland, AL, Hafizi, S, Tseng, HH, Holmes, SE, Hinz, R, Drake, RJ, Yaqub, M, Schuitemaker, A, Edison, P, Pavese, N, Lockhart, A, Davis, B, Matthews, JC, Quarantelli, M, Laule, C, Vavasour, IM, Kolind, SH, Pasternak, O, Sochen, N, Gur, Y, Intrator, N, Assaf, Y, Andreasen, NC, Ehrhardt, JC, Swayze, VW, Supprian, T, Hofmann, E, Warmuth-Metz, M, Franzek, E, Becker, T, Pfefferbaum, A, Sullivan, EV, Hedehus, M, Moseley, M, Lim, KO, Mandl, RC, Schnack, HG, Luigjes, J, Cahn, W, Bagary, MS, Symms, MR, Barker, GJ, Mutsatsa, SH, Joyce, EM, Ron, MA, Foong, J, Maier, M, Brocklehurst, S, Miller, DH, Kubicki, M, Park, H, Westin, CF, Bouix, S, Dahlben, B, Oestreich, LK, Shenton, ME, Amato, D, Beasley, CL, Hahn, MK, Vernon, AC, Natesan, S, Modo, M, Kapur, S, Mondelli, V, Reininghaus, U, Kempton, MJ, Valmaggia, L, Baumeister, D, Lightman, SL, Pariante, CM, Danese, A, Moffitt, TE, Ambler, A, Poulton, R, Caspi, A, Akhtar, R, Ciufolini, S, Meyer, U, So, PW, Lythgoe, DJ, Cotel, MC, Lenartowicz, EM, Anacker, C, Calcia, MA, Bonsall, DR, Barichello, T, Howes, OD, Burke, NN, Fan, CY, Trang, T, McMahon, SB, Russa, F La, Bennett, DL, Püntener, U, Booth, SG, Perry, VH, Teeling, JL, Hahn, YK, Podhaizer, EM, Farris, SP, Miles, MF, Hauser, KF, Knapp, PE, Notter, T, Gschwind, T, Varga, B, Markó, K, Hádinger, N, Cattaneo, A, Ferrari, C, Uher, R, Belvederi, Murri M, Sandiego, CM, Pittman, B, Weber, MD, Sheridan, JF, Raison, CL, Rutherford, RE, Woolwine, BJ, Möller, T, Boddeke, HW, O'Connor, JC, Lawson, MA, André, C, Hinwood, M, Morandini, J, Day, TA, Walker, FR, Bard, F, Bhattacharya, A, Pae, CU, Marks, DM, Han, C, Patkar, AA, Oya, K, Kishi, T, Iwata, N, Pathology, NCA - Neuroinflamation, Molecular cell biology and Immunology, Gastroenterology and hepatology, CCA - Disease profiling, ICaR - Heartfailure and pulmonary arterial hypertension, ICaR - Ischemia and repair, NCA - Brain imaging technology, Radiology and nuclear medicine, Amsterdam Neuroscience - Brain Imaging, Otolaryngology / Head & Neck Surgery, EMGO - Quality of care, AII - Infectious diseases, CCA - Imaging, and Neurology
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0301 basic medicine ,medicine.medical_specialty ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Animals ,Humans ,Psychology ,In patient ,Psychiatry ,Biological Psychiatry ,Neuroinflammation ,Inflammation ,Microglia ,business.industry ,Macrophages ,Mental Disorders ,Brain ,Magnetic Resonance Imaging ,Psychiatry and Mental health ,030104 developmental biology ,medicine.anatomical_structure ,Psychosocial stress ,Treatment strategy ,Autopsy ,business ,Neuroscience ,030217 neurology & neurosurgery ,Stress, Psychological ,Immune activation - Abstract
SummaryThe role of immune activation in psychiatric disorders has attracted considerable attention over the past two decades, contributing to the rise of a new era for psychiatry. Microglia, the macrophages of the brain, are progressively becoming the main focus of the research in this field. In this Review, we assess the literature on microglia activation across different psychiatric disorders, including post-mortem and in-vivo studies in humans and experimental studies in animals. Although microglia activation has been noted in all types of psychiatric disorder, no association was seen with specific diagnostic categories. Furthermore, the findings from these studies highlight that not all psychiatric patients have microglial activation. Therefore, the cause of the neuroinflammation in these cohorts and its implications are unclear. We discuss psychosocial stress as one of the main factors determining microglial activation in patients with psychiatric disorders, and explore the relevance of these findings for future treatment strategies.
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- 2016
3. Translational evaluation of translocator protein as a marker of neuroinflammation in schizophrenia
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Notter, T, primary, Coughlin, J M, additional, Gschwind, T, additional, Weber-Stadlbauer, U, additional, Wang, Y, additional, Kassiou, M, additional, Vernon, A C, additional, Benke, D, additional, Pomper, M G, additional, Sawa, A, additional, and Meyer, U, additional
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- 2017
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4. Hypervulnerability of the adolescent prefrontal cortex to nutritional stress via reelin deficiency
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Labouesse, M A, primary, Lassalle, O, additional, Richetto, J, additional, Iafrati, J, additional, Weber-Stadlbauer, U, additional, Notter, T, additional, Gschwind, T, additional, Pujadas, L, additional, Soriano, E, additional, Reichelt, A C, additional, Labouesse, C, additional, Langhans, W, additional, Chavis, P, additional, and Meyer, U, additional
- Published
- 2016
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5. IBM Secure Enterprise Desktop
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Baentsch, M., primary, Buhler, P., additional, Garces-Erice, L., additional, Gschwind, T., additional, Horing, F., additional, Kuyper, M., additional, Schade, A., additional, Scotton, P., additional, and Urbanetz, P., additional
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- 2014
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6. Translational evaluation of translocator protein as a marker of neuroinflammation in schizophrenia
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Notter, T, Coughlin, J M, Gschwind, T, Weber-Stadlbauer, U, Wang, Y, Kassiou, M, Vernon, A C, Benke, D, Pomper, M G, Sawa, A, and Meyer, U
- Abstract
Positron emission tomography (PET) imaging with radiotracers that target translocator protein 18 kDa (TSPO) has become a popular approach to assess putative neuroinflammatory processes and associated microglia activation in psychotic illnesses. It remains unclear, however, whether TSPO imaging can accurately capture low-grade inflammatory processes such as those present in schizophrenia and related disorders. Therefore, we evaluated the validity of TSPO as a disease-relevant marker of inflammation using a translational approach, which combined neurodevelopmental and neurodegenerative mouse models with PET imaging in patients with recent-onset schizophrenia and matched controls. Using an infection-mediated neurodevelopmental mouse model, we show that schizophrenia-relevant behavioral abnormalities and increased inflammatory cytokine expression are associated with reduced prefrontal TSPO levels. On the other hand, TSPO was markedly upregulated in a mouse model of acute neurodegeneration and reactive gliosis, which was induced by intrahippocampal injection of kainic acid. In both models, the changes in TSPO levels were not restricted to microglia but emerged in various cell types, including microglia, astrocytes and vascular endothelial cells. Human PET imaging using the second-generation TSPO radiotracer [11C]DPA-713 revealed a strong trend towards reduced TSPO binding in the middle frontal gyrus of patients with recent-onset schizophrenia, who were previously shown to display increased levels of inflammatory cytokines in peripheral and central tissues. Together, our findings challenge the common assumption that central low-grade inflammation in schizophrenia is mirrored by increased TSPO expression or ligand binding. Our study further underscores the need to interpret altered TSPO binding in schizophrenia with caution, especially when measures of TSPO are not complemented with other markers of inflammation. Unless more selective microglial markers are available for PET imaging, quantification of cytokines and other inflammatory biomarkers, along with their molecular signaling pathways, may be more accurate in attempts to characterize inflammatory profiles in schizophrenia and other mental disorders that lack robust reactive gliosis.
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- 2018
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7. Extracting Interactions in Component-Based Systems
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Parsons, T., primary, Mos, A., additional, Trofin, M., additional, Gschwind, T., additional, and Murphy, J., additional
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- 2008
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8. ShareMe: Running a Distributed Systems Lab for 600 Students With Three Faculty Members
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Kerer, C., primary, Reif, G., additional, Gschwind, T., additional, Kirda, E., additional, Kurmanowytsch, R., additional, and Paralic, M., additional
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- 2005
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9. Combining Pattern Languages and Reusable Architectural Decision Models into a Comprehensive and Comprehensible Design Method.
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Zimmermann, O., Zdun, U., Gschwind, T., and Leymann, F.
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- 2008
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10. System evolution tracking through execution trace analysis.
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Fischer, M., Oberleitner, J., Gall, H., and Gschwind, T.
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- 2005
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11. TUAnalyzer - analyzing templates in C++ code.
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Gschwind, T., Pinzger, M., and Gall, H.
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- 2004
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12. Using run-time data for program comprehension.
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Gschwind, T., Oberleitner, J., and Pinzger, M.
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- 2003
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13. Improving dynamic data analysis with aspect-oriented programming.
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Gschwind, T. and Oberleitner, J.
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- 2003
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14. WebMon: A performance profiler for web transactions.
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Gschwind, T., Eshghi, K., Garg, P.K., and Wurster, K.
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- 2002
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15. ADK-building mobile agents for network and systems management from reusable components.
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Gschwind, T., Feridun, M., and Pleisch, S.
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- 1999
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16. WebMon: A performance profiler for web transactions
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Gschwind, T., primary, Eshghi, K., additional, Garg, P.K., additional, and Wurster, K., additional
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17. Improving dynamic data analysis with aspect-oriented programming
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Gschwind, T., primary and Oberleitner, J., additional
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18. TUAnalyzer - analyzing templates in C++ code
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Gschwind, T., primary, Pinzger, M., additional, and Gall, H., additional
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19. Using run-time data for program comprehension
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Gschwind, T., primary, Oberleitner, J., additional, and Pinzger, M., additional
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20. System Evolution Tracking through Execution Trace Analysis
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Fischer, M., primary, Oberleitner, J., additional, Gall, H., additional, and Gschwind, T., additional
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21. Experience with lightweight distributed component technologies in Business Intelligence systems
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Tony Wicks, Leticia Duboc, Wolfgang Emmerich, Gschwind, T, and Mascolo, C
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Decision support system ,Java ,business.industry ,Event (computing) ,Computer science ,Database schema ,Science & Technology, Technology, Computer Science, Software Engineering, Computer Science, Theory & Methods, Computer Science ,Data modeling ,Management information systems ,Data model ,Analytics ,Component (UML) ,Business intelligence ,Software engineering ,business ,Transaction data ,computer ,computer.programming_language - Abstract
Business Intelligence (BI) systems address the demands of large scale enterprises for operational analytics, management information and decision support tasks. Building such applications presents many challenges. They must support complex and changing data models, have fast turnarounds, present an up-to-date and accurate view of information and provide extensibility mechanisms for new analyses. Widely adopted distributed object systems, such as J2EE can be heavyweight and inflexible when applied to the described scenario. This paper presents our experience when developing a data analysis system that applies a combination of lightweight distributed component technologies available for Java. These technologies are combined in an event-based architecture that anticipates constant changes to analysis algorithms in short time frames and provides the ability to maintain correlated analyses in a consistent state. The resulting architecture is extensible, easy to deploy, highly configurable and has a very flexible data model. We compare this approach with existing distributed object systems and evaluate its suitability to provide business intelligence.
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- 2005
22. Acetylcholine receptor based chemogenetics engineered for neuronal inhibition and seizure control assessed in mice.
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Nguyen QA, Klein PM, Xie C, Benthall KN, Iafrati J, Homidan J, Bendor JT, Dudok B, Farrell JS, Gschwind T, Porter CL, Keravala A, Dodson GS, and Soltesz I
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- Mice, Male, Humans, Animals, Receptors, Cholinergic, alpha7 Nicotinic Acetylcholine Receptor genetics, Nicotinic Agonists pharmacology, Acetylcholine pharmacology, Seizures genetics, Receptors, Nicotinic genetics, Epilepsy
- Abstract
Epilepsy is a prevalent disorder involving neuronal network hyperexcitability, yet existing therapeutic strategies often fail to provide optimal patient outcomes. Chemogenetic approaches, where exogenous receptors are expressed in defined brain areas and specifically activated by selective agonists, are appealing methods to constrain overactive neuronal activity. We developed BARNI (Bradanicline- and Acetylcholine-activated Receptor for Neuronal Inhibition), an engineered channel comprised of the α7 nicotinic acetylcholine receptor ligand-binding domain coupled to an α1 glycine receptor anion pore domain. Here we demonstrate that BARNI activation by the clinical stage α7 nicotinic acetylcholine receptor-selective agonist bradanicline effectively suppressed targeted neuronal activity, and controlled both acute and chronic seizures in male mice. Our results provide evidence for the use of an inhibitory acetylcholine-based engineered channel activatable by both exogenous and endogenous agonists as a potential therapeutic approach to treating epilepsy., (© 2024. The Author(s).)
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- 2024
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23. Artificial intelligence in epilepsy phenotyping.
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Knight A, Gschwind T, Galer P, Worrell GA, Litt B, Soltesz I, and Beniczky S
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Artificial intelligence (AI) allows data analysis and integration at an unprecedented granularity and scale. Here we review the technological advances, challenges, and future perspectives of using AI for electro-clinical phenotyping of animal models and patients with epilepsy. In translational research, AI models accurately identify behavioral states in animal models of epilepsy, allowing identification of correlations between neural activity and interictal and ictal behavior. Clinical applications of AI-based automated and semi-automated analysis of audio and video recordings of people with epilepsy, allow significant data reduction and reliable detection and classification of major motor seizures. AI models can accurately identify electrographic biomarkers of epilepsy, such as spikes, high-frequency oscillations, and seizure patterns. Integrating AI analysis of electroencephalographic, clinical, and behavioral data will contribute to optimizing therapy for patients with epilepsy., (© 2023 International League Against Epilepsy.)
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- 2023
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24. Hidden behavioral fingerprints in epilepsy.
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Gschwind T, Zeine A, Raikov I, Markowitz JE, Gillis WF, Felong S, Isom LL, Datta SR, and Soltesz I
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- Animals, Mice, Disease Models, Animal, Brain, Epilepsy genetics
- Abstract
Epilepsy is a major disorder affecting millions of people. Although modern electrophysiological and imaging approaches provide high-resolution access to the multi-scale brain circuit malfunctions in epilepsy, our understanding of how behavior changes with epilepsy has remained rudimentary. As a result, screening for new therapies for children and adults with devastating epilepsies still relies on the inherently subjective, semi-quantitative assessment of a handful of pre-selected behavioral signs of epilepsy in animal models. Here, we use machine learning-assisted 3D video analysis to reveal hidden behavioral phenotypes in mice with acquired and genetic epilepsies and track their alterations during post-insult epileptogenesis and in response to anti-epileptic drugs. These results show the persistent reconfiguration of behavioral fingerprints in epilepsy and indicate that they can be employed for rapid, automated anti-epileptic drug testing at scale., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)
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- 2023
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25. Ripple-selective GABAergic projection cells in the hippocampus.
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Szabo GG, Farrell JS, Dudok B, Hou WH, Ortiz AL, Varga C, Moolchand P, Gulsever CI, Gschwind T, Dimidschstein J, Capogna M, and Soltesz I
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- Animals, Mice, Neurons physiology, Parvalbumins, Wakefulness, Hippocampus physiology, Interneurons physiology
- Abstract
Ripples are brief high-frequency electrographic events with important roles in episodic memory. However, the in vivo circuit mechanisms coordinating ripple-related activity among local and distant neuronal ensembles are not well understood. Here, we define key characteristics of a long-distance projecting GABAergic cell group in the mouse hippocampus that selectively exhibits high-frequency firing during ripples while staying largely silent during theta-associated states when most other GABAergic cells are active. The high ripple-associated firing commenced before ripple onset and reached its maximum before ripple peak, with the signature theta-OFF, ripple-ON firing pattern being preserved across awake and sleep states. Controlled by septal GABAergic, cholinergic, and CA3 glutamatergic inputs, these ripple-selective cells innervate parvalbumin and cholecystokinin-expressing local interneurons while also targeting a variety of extra-hippocampal regions. These results demonstrate the existence of a hippocampal GABAergic circuit element that is uniquely positioned to coordinate ripple-related neuronal dynamics across neuronal assemblies., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)
- Published
- 2022
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26. Supramammillary regulation of locomotion and hippocampal activity.
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Farrell JS, Lovett-Barron M, Klein PM, Sparks FT, Gschwind T, Ortiz AL, Ahanonu B, Bradbury S, Terada S, Oijala M, Hwaun E, Dudok B, Szabo G, Schnitzer MJ, Deisseroth K, Losonczy A, and Soltesz I
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- Action Potentials, Animals, Hippocampus cytology, Hypothalamus, Posterior cytology, Mice, Mice, Inbred C57BL, Neural Pathways physiology, Rats, Spatial Navigation, Substance P genetics, Theta Rhythm, Hippocampus physiology, Hypothalamus, Posterior physiology, Locomotion, Neurons physiology
- Abstract
Locomotor speed is a basic input used to calculate one’s position, but where this signal comes from is unclear. We identified neurons in the supramammillary nucleus (SuM) of the rodent hypothalamus that were highly correlated with future locomotor speed and reliably drove locomotion when activated. Robust locomotion control was specifically identified in Tac1 (substance P)–expressing (SuM
Tac1+ ) neurons, the activation of which selectively controlled the activity of speed-modulated hippocampal neurons. By contrast, Tac1 -deficient (SuMTac1− ) cells weakly regulated locomotion but potently controlled the spike timing of hippocampal neurons and were sufficient to entrain local network oscillations. These findings emphasize that the SuM not only regulates basic locomotor activity but also selectively shapes hippocampal neural activity in a manner that may support spatial navigation.- Published
- 2021
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27. Optogenetic intervention of seizures improves spatial memory in a mouse model of chronic temporal lobe epilepsy.
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Kim HK, Gschwind T, Nguyen TM, Bui AD, Felong S, Ampig K, Suh D, Ciernia AV, Wood MA, and Soltesz I
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- Animals, Channelrhodopsins, Chronic Disease, Cognitive Dysfunction psychology, Cognitive Dysfunction therapy, Disease Models, Animal, Electroencephalography, Epilepsy, Temporal Lobe chemically induced, Epilepsy, Temporal Lobe psychology, Epilepsy, Temporal Lobe therapy, Excitatory Amino Acid Agonists toxicity, Hippocampus, Kainic Acid toxicity, Mice, Parvalbumins, Video Recording, Cognitive Dysfunction physiopathology, Epilepsy, Temporal Lobe physiopathology, Interneurons, Optogenetics methods, Spatial Learning, Spatial Memory
- Abstract
Objective: To determine if closed-loop optogenetic seizure intervention, previously shown to reduce seizure duration in a well-established mouse model chronic temporal lobe epilepsy (TLE), also improves the associated comorbidity of impaired spatial memory., Methods: Mice with chronic, spontaneous seizures in the unilateral intrahippocampal kainic acid model of TLE, expressing channelrhodopsin in parvalbumin-expressing interneurons, were implanted with optical fibers and electrodes, and tested for response to closed-loop light intervention of seizures. Animals that responded to closed-loop optogenetic curtailment of seizures were tested in the object location memory test and then given closed-loop optogenetic intervention on all detected seizures for 2 weeks. Following this, they were tested with a second object location memory test, with different objects and contexts than used previously, to assess if seizure suppression can improve deficits in spatial memory., Results: Animals that received closed-loop optogenetic intervention performed significantly better in the second object location memory test compared to the first test. Epileptic controls with no intervention showed stable frequency and duration of seizures, as well as stable spatial memory deficits, for several months after the precipitating insult., Significance: Many currently available treatments for epilepsy target seizures but not the associated comorbidities, therefore there is a need to investigate new potential therapies that may be able to improve both seizure burden and associated comorbidities of epilepsy. In this study, we showed that optogenetic intervention may be able to both shorten seizure duration and improve cognitive outcomes of spatial memory., (Wiley Periodicals, Inc. © 2020 International League Against Epilepsy.)
- Published
- 2020
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28. Aberrant expression of PAR bZIP transcription factors is associated with epileptogenesis, focus on hepatic leukemia factor.
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Rambousek L, Gschwind T, Lafourcade C, Paterna JC, Dib L, Fritschy JM, and Fontana A
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- Animals, Dentate Gyrus pathology, Disease Models, Animal, Epilepsy chemically induced, Kainic Acid adverse effects, Kainic Acid pharmacology, Male, Mice, Basic-Leucine Zipper Transcription Factors metabolism, Dentate Gyrus metabolism, Epilepsy metabolism, Gene Expression Regulation
- Abstract
Epilepsy is a widespread neurological disease characterized by abnormal neuronal activity resulting in recurrent seizures. There is mounting evidence that a circadian system disruption, involving clock genes and their downstream transcriptional regulators, is associated with epilepsy. In this study, we characterized the hippocampal expression of clock genes and PAR bZIP transcription factors (TFs) in a mouse model of temporal lobe epilepsy induced by intrahippocampal injection of kainic acid (KA). The expression of PAR bZIP TFs was significantly altered following KA injection as well as in other rodent models of acquired epilepsy. Although the PAR bZIP TFs are regulated by proinflammatory cytokines in peripheral tissues, we discovered that the regulation of their expression is inflammation-independent in hippocampal tissue and rather mediated by clock genes and hyperexcitability. Furthermore, we report that hepatic leukemia factor (Hlf), a member of PAR bZIP TFs family, is invariably downregulated in animal models of acquired epilepsy, regulates neuronal activity in vitro and its overexpression in dentate gyrus neurons in vivo leads to altered expression of genes associated with seizures and epilepsy. Overall, our study provides further evidence of PAR bZIP TFs involvement in epileptogenesis and points to Hlf as the key player.
- Published
- 2020
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29. Contribution of early Alzheimer's disease-related pathophysiology to the development of acquired epilepsy.
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Gschwind T, Lafourcade C, Gfeller T, Zaichuk M, Rambousek L, Knuesel I, and Fritschy JM
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- Animals, CA1 Region, Hippocampal metabolism, CA1 Region, Hippocampal physiopathology, Dentate Gyrus metabolism, Dentate Gyrus physiopathology, Disease Models, Animal, Electroencephalography, Excitatory Amino Acid Agonists pharmacology, Kainic Acid pharmacology, Male, Mice, Mice, Transgenic, Status Epilepticus metabolism, Status Epilepticus physiopathology, Alzheimer Disease metabolism, Alzheimer Disease physiopathology, Amyloid beta-Peptides metabolism, Epilepsy, Temporal Lobe metabolism, Epilepsy, Temporal Lobe physiopathology, Hippocampus metabolism, Hippocampus physiopathology, Neuronal Plasticity physiology, Seizures metabolism, Seizures physiopathology
- Abstract
Aberrant epileptic activity is detectable at early disease stages in Alzheimer's disease (AD) patients and in AD mouse models. Here, we investigated in young ArcticAβ mice whether AD-like pathology renders neuronal networks more susceptible to the development of acquired epilepsy induced by unilateral intrahippocampal injection of kainic acid (IHK). In this temporal lobe epilepsy model, IHK induces a status epilepticus followed after two weeks by spontaneous recurrent seizures (SRS). ArcticAβ mice exhibited more severe status epilepticus and early onset of SRS. This hyperexcitable phenotype was characterized in CA1 neurons by decreased synaptic strength, increased kainic acid-induced LTP and reduced frequency of spontaneous inhibitory currents. However, no difference in neurodegeneration, neuroinflammation, axonal reorganization or adult neurogenesis was observed in ArcticAβ mice compared to wild-type littermates following IHK-induced epileptogenesis. Neuropeptide Y (NPY) expression was reduced at baseline and its IHK-induced elevation in mossy fibres and granule cells was attenuated. However, although this alteration might underlie premature seizure onset, neutralization of soluble Aβ species by intracerebroventricular Aβ-specific antibody application mitigated the hyperexcitable phenotype of ArcticAβ mice and prevented early SRS onset. Therefore, the development of seizures at early stages of AD is mediated primarily by Aβ species causing widespread changes in synaptic function., (© 2018 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)
- Published
- 2018
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30. Establishing a learned-helplessness effect paradigm in C57BL/6 mice: behavioural evidence for emotional, motivational and cognitive effects of aversive uncontrollability per se.
- Author
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Pryce CR, Azzinnari D, Sigrist H, Gschwind T, Lesch KP, and Seifritz E
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- Analysis of Variance, Animals, Conditioning, Classical physiology, Electroshock adverse effects, Escape Reaction, Female, Male, Mice, Mice, Inbred C57BL, Mice, Knockout, Pain Perception physiology, Random Allocation, Serotonin Plasma Membrane Transport Proteins deficiency, Avoidance Learning physiology, Cognition physiology, Emotions, Helplessness, Learned, Motivation physiology
- Abstract
Uncontrollability of major life events has been proposed to be central to depression onset and maintenance. The learned helplessness (LH) effect describes a deficit in terminating controllable aversive stimuli in individuals that experienced aversive stimuli as uncontrollable relative to individuals that experienced the same stimuli as controllable. The LH effect translates across species and therefore can provide an objective-valid readout in animal models of depression. Paradigms for a robust LH effect are established and currently applied in rat but there are few reports of prior and current study of the LH effect in mouse. This includes the C57BL/6 mouse, typically the strain of choice for application of molecular-genetic tools in pre-clinical depression research. The aims of this study were to develop a robust paradigm for the LH effect in BL/6 mice, provide evidence for underlying psychological processes, and study the effect of a depression-relevant genotype on the LH effect. The apparatus used for in/escapable electro-shock exposure and escape test was a two-way shuttle arena with continuous automated measurement of locomotion, compartment transfers, e-shock escapes, vertical activity and freezing. Brother-pairs of BL/6 mice were allocated to either escapable e-shocks (ES) or inescapable e-shocks (IS), with escape latencies of the ES brother used as e-shock durations for the IS brother. The standard two-way shuttle paradigm was modified: the central gate was replaced by a raised divider and e-shock escape required transfer to the distal part of the safe compartment. These refinements yielded reduced superstitious, pre-adaptive e-shock transfers in IS mice and thereby increased the LH effect. To obtain a robust LH effect in all brother pairs, pre-screening for minor between-brother ES differences was necessary and did not confound the LH effect. IS mice developed reduced motor responses to e-shock, consistent with a motivational deficit, and absence of a learning curve for escapes at escape test, consistent with a cognitive deficit. When a tone CS was used to predict e-shock, IS mice exhibited increased reactivity to the CS, consistent with hyper-emotionality. There was no ES-IS difference in pain sensitivity. Mice heterozygous knockout for the 5-HTT gene exhibited an increased LH effect relative to wildtype mice. This mouse model will allow for the detailed molecular study of the aetiology, psychology, neurobiology and neuropharmacology of uncontrollability of aversive stimuli, a potential major aetiological factor and state marker in depression. This article is part of a Special Issue entitled 'Anxiety and Depression'., (Copyright © 2011 Elsevier Ltd. All rights reserved.)
- Published
- 2012
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31. [Estrogen substitution using a transdermal system].
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Schenkel L, Barlier D, Gay C, and Gschwind T
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- Administration, Cutaneous, Administration, Oral, Estradiol pharmacokinetics, Female, Gels, Humans, Menopause, Estradiol administration & dosage
- Published
- 1988
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