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1. Glial Bmal1 role in mammalian retina daily changes

Author

Serena Riccitelli, Fabio Boi, Davide Lonardoni, Lidia Giantomasi, Olga Barca-Mayo, Davide De Pietri Tonelli, Silvia Bisti, Stefano Di Marco, and Luca Berdondini

Subjects
Medicine, Science
Abstract

Abstract Visual information processing in the retina requires the rhythmic expression of clock genes. The intrinsic retinal circadian clock is independent of the master clock located in the hypothalamic suprachiasmatic nucleus and emerges from retinal cells, including glia. Less clear is how glial oscillators influence the daily regulation of visual information processing in the mouse retina. Here, we demonstrate that the adult conditional deletion of the gene Bmal1 in GLAST-positive glial cells alters retinal physiology. Specifically, such deletion was sufficient to lower the amplitude of the electroretinogram b-wave recorded under light-adapted conditions. Furthermore, recordings from > 20,000 retinal ganglion cells (RGCs), the retina output, showed a non-uniform effect on RGCs activity in response to light across different cell types and over a 24-h period. Overall, our results suggest a new role of a glial circadian gene in adjusting mammalian retinal output throughout the night-day cycle.

Published
2022
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2. 26th Annual Computational Neuroscience Meeting (CNS*2017): Part 2

Author

Leonid L. Rubchinsky, Sungwoo Ahn, Wouter Klijn, Ben Cumming, Stuart Yates, Vasileios Karakasis, Alexander Peyser, Marmaduke Woodman, Sandra Diaz-Pier, James Deraeve, Eliana Vassena, William Alexander, David Beeman, Pawel Kudela, Dana Boatman-Reich, William S. Anderson, Niceto R. Luque, Francisco Naveros, Richard R. Carrillo, Eduardo Ros, Angelo Arleo, Jacob Huth, Koki Ichinose, Jihoon Park, Yuji Kawai, Junichi Suzuki, Hiroki Mori, Minoru Asada, Sorinel A. Oprisan, Austin I. Dave, Tahereh Babaie, Peter Robinson, Alejandro Tabas, Martin Andermann, André Rupp, Emili Balaguer-Ballester, Henrik Lindén, Rasmus K. Christensen, Mari Nakamura, Tania R. Barkat, Zach Tosi, John Beggs, Davide Lonardoni, Fabio Boi, Stefano Di Marco, Alessandro Maccione, Luca Berdondini, Joanna Jędrzejewska-Szmek, Daniel B. Dorman, Kim T. Blackwell, Christoph Bauermeister, Hanna Keren, Jochen Braun, João V. Dornas, Eirini Mavritsaki, Silvio Aldrovandi, Emma Bridger, Sukbin Lim, Nicolas Brunel, Anatoly Buchin, Clifford Charles Kerr, Anton Chizhov, Gilles Huberfeld, Richard Miles, Boris Gutkin, Martin J. Spencer, Hamish Meffin, David B. Grayden, Anthony N. Burkitt, Catherine E. Davey, Liangyu Tao, Vineet Tiruvadi, Rehman Ali, Helen Mayberg, Robert Butera, Cengiz Gunay, Damon Lamb, Ronald L. Calabrese, Anca Doloc-Mihu, Víctor J. López-Madrona, Fernanda S. Matias, Ernesto Pereda, Claudio R. Mirasso, Santiago Canals, Alice Geminiani, Alessandra Pedrocchi, Egidio D’Angelo, Claudia Casellato, Ankur Chauhan, Karthik Soman, V. Srinivasa Chakravarthy, Vignayanandam R. Muddapu, Chao-Chun Chuang, Nan-yow Chen, Mehdi Bayati, Jan Melchior, Laurenz Wiskott, Amir Hossein Azizi, Kamran Diba, Sen Cheng, Elena Y. Smirnova, Elena G. Yakimova, Anton V. Chizhov, Nan-Yow Chen, Chi-Tin Shih, Dorian Florescu, Daniel Coca, Julie Courtiol, Viktor K. Jirsa, Roberto J. M. Covolan, Bartosz Teleńczuk, Richard Kempter, Gabriel Curio, Alain Destexhe, Jessica Parker, Alexander N. Klishko, Boris I. Prilutsky, Gennady Cymbalyuk, Felix Franke, Andreas Hierlemann, Rava Azeredo da Silveira, Stefano Casali, Stefano Masoli, Martina Rizza, Martina Francesca Rizza, Yinming Sun, Willy Wong, Faranak Farzan, Daniel M. Blumberger, Zafiris J. Daskalakis, Svitlana Popovych, Shivakumar Viswanathan, Nils Rosjat, Christian Grefkes, Silvia Daun, Damiano Gentiletti, Piotr Suffczynski, Vadym Gnatkovski, Marco De Curtis, Hyeonsu Lee, Se-Bum Paik, Woochul Choi, Jaeson Jang, Youngjin Park, Jun Ho Song, Min Song, Vicente Pallarés, Matthieu Gilson, Simone Kühn, Andrea Insabato, Gustavo Deco, Katharina Glomb, Adrián Ponce-Alvarez, Petra Ritter, Adria Tauste Campo, Alexander Thiele, Farah Deeba, P. A. Robinson, Sacha J. van Albada, Andrew Rowley, Michael Hopkins, Maximilian Schmidt, Alan B. Stokes, David R. Lester, Steve Furber, Markus Diesmann, Alessandro Barri, Martin T. Wiechert, David A. DiGregorio, Alexander G. Dimitrov, Catalina Vich, Rune W. Berg, Antoni Guillamon, Susanne Ditlevsen, Romain D. Cazé, Benoît Girard, Stéphane Doncieux, Nicolas Doyon, Frank Boahen, Patrick Desrosiers, Edward Laurence, Louis J. Dubé, Russo Eleonora, Daniel Durstewitz, Dominik Schmidt, Tuomo Mäki-Marttunen, Florian Krull, Francesco Bettella, Christoph Metzner, Anna Devor, Srdjan Djurovic, Anders M. Dale, Ole A. Andreassen, Gaute T. Einevoll, Solveig Næss, Torbjørn V. Ness, Geir Halnes, Eric Halgren, Klas H. Pettersen, Marte J. Sætra, Espen Hagen, Alina Schiffer, Axel Grzymisch, Malte Persike, Udo Ernst, Daniel Harnack, Udo A. Ernst, Nergis Tomen, Stefano Zucca, Valentina Pasquale, Giuseppe Pica, Manuel Molano-Mazón, Michela Chiappalone, Stefano Panzeri, Tommaso Fellin, Kelvin S. Oie, David L. Boothe, Joshua C. Crone, Alfred B. Yu, Melvin A. Felton, Isma Zulfiqar, Michelle Moerel, Peter De Weerd, Elia Formisano, Kelvin Oie, Piotr Franaszczuk, Roland Diggelmann, Michele Fiscella, Domenico Guarino, Jan Antolík, Andrew P. Davison, Yves Frègnac, Benjamin Xavier Etienne, Flavio Frohlich, Jérémie Lefebvre, Encarni Marcos, Maurizio Mattia, Aldo Genovesio, Leonid A. Fedorov, Tjeerd M.H. Dijkstra, Louisa Sting, Howard Hock, Martin A. Giese, Laure Buhry, Clément Langlet, Francesco Giovannini, Christophe Verbist, Stefano Salvadé, Michele Giugliano, James A. Henderson, Hendrik Wernecke, Bulcsú Sándor, Claudius Gros, Nicole Voges, Paulina Dabrovska, Alexa Riehle, Thomas Brochier, Sonja Grün, Yifan Gu, Pulin Gong, Grégory Dumont, Nikita A. Novikov, Boris S. Gutkin, Parul Tewatia, Olivia Eriksson, Andrei Kramer, Joao Santos, Alexandra Jauhiainen, Jeanette H. Kotaleski, Jovana J. Belić, Arvind Kumar, Jeanette Hellgren Kotaleski, Masanori Shimono, Naomichi Hatano, Subutai Ahmad, Yuwei Cui, Jeff Hawkins, Johanna Senk, Karolína Korvasová, Tom Tetzlaff, Moritz Helias, Tobias Kühn, Michael Denker, PierGianLuca Mana, David Dahmen, Jannis Schuecker, Sven Goedeke, Christian Keup, Katja Heuer, Rembrandt Bakker, Paul Tiesinga, Roberto Toro, Wei Qin, Alex Hadjinicolaou, Michael R. Ibbotson, Tatiana Kameneva, William W. Lytton, Lealem Mulugeta, Andrew Drach, Jerry G. Myers, Marc Horner, Rajanikanth Vadigepalli, Tina Morrison, Marlei Walton, Martin Steele, C. Anthony Hunt, Nicoladie Tam, Rodrigo Amaducci, Carlos Muñiz, Manuel Reyes-Sánchez, Francisco B. Rodríguez, Pablo Varona, Joseph T. Cronin, Matthias H. Hennig, Elisabetta Iavarone, Jane Yi, Ying Shi, Bas-Jan Zandt, Werner Van Geit, Christian Rössert, Henry Markram, Sean Hill, Christian O’Reilly, Rodrigo Perin, Huanxiang Lu, Alexander Bryson, Michal Hadrava, Jaroslav Hlinka, Ryosuke Hosaka, Mark Olenik, Conor Houghton, Nicolangelo Iannella, Thomas Launey, Rebecca Kotsakidis, Jaymar Soriano, Takatomi Kubo, Takao Inoue, Hiroyuki Kida, Toshitaka Yamakawa, Michiyasu Suzuki, Kazushi Ikeda, Samira Abbasi, Amber E. Hudson, Detlef H. Heck, Dieter Jaeger, Joel Lee, Skirmantas Janušonis, Maria Luisa Saggio, Andreas Spiegler, William C. Stacey, Christophe Bernard, Davide Lillo, Spase Petkoski, Mark Drakesmith, Derek K. Jones, Ali Sadegh Zadeh, Chandra Kambhampati, Jan Karbowski, Zeynep Gokcen Kaya, Yair Lakretz, Alessandro Treves, Lily W. Li, Joseph Lizier, Cliff C. Kerr, Timothée Masquelier, Saeed Reza Kheradpisheh, Hojeong Kim, Chang Sub Kim, Julia A. Marakshina, Alexander V. Vartanov, Anastasia A. Neklyudova, Stanislav A. Kozlovskiy, Andrey A. Kiselnikov, Kanako Taniguchi, Katsunori Kitano, Oliver Schmitt, Felix Lessmann, Sebastian Schwanke, Peter Eipert, Jennifer Meinhardt, Julia Beier, Kanar Kadir, Adrian Karnitzki, Linda Sellner, Ann-Christin Klünker, Lena Kuch, Frauke Ruß, Jörg Jenssen, Andreas Wree, Paula Sanz-Leon, Stuart A. Knock, Shih-Cheng Chien, Burkhard Maess, Thomas R. Knösche, Charles C. Cohen, Marko A. Popovic, Jan Klooster, Maarten H.P. Kole, Erik A. Roberts, Nancy J. Kopell, Daniel Kepple, Hamza Giaffar, Dima Rinberg, Alex Koulakov, Caroline Garcia Forlim, Leonie Klock, Johanna Bächle, Laura Stoll, Patrick Giemsa, Marie Fuchs, Nikola Schoofs, Christiane Montag, Jürgen Gallinat, Ray X. Lee, Greg J. Stephens, Bernd Kuhn, Luiz Tauffer, Philippe Isope, Katsuma Inoue, Yoshiyuki Ohmura, Shogo Yonekura, Yasuo Kuniyoshi, Hyun Jae Jang, Jeehyun Kwag, Marc de Kamps, Yi Ming Lai, Filipa dos Santos, K. P. Lam, Peter Andras, Julia Imperatore, Jessica Helms, Tamas Tompa, Antonieta Lavin, Felicity H. Inkpen, Michael C. Ashby, Nathan F. Lepora, Aaron R. Shifman, John E. Lewis, Zhong Zhang, Yeqian Feng, Christian Tetzlaff, Tomas Kulvicius, Yinyun Li, Rodrigo F. O. Pena, Davide Bernardi, Antonio C. Roque, Benjamin Lindner, Sebastian Vellmer, Ausra Saudargiene, Tiina Maninen, Riikka Havela, Marja-Leena Linne, Arthur Powanwe, Andre Longtin, Jesús A. Garrido, Joe W. Graham, Salvador Dura-Bernal, Sergio L. Angulo, Samuel A. Neymotin, and Srdjan D. Antic

Subjects
Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571, Neurophysiology and neuropsychology, QP351-495
Published
2017
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3. 26th Annual Computational Neuroscience Meeting (CNS*2017): Part 3

Author

Adam J. H. Newton, Alexandra H. Seidenstein, Robert A. McDougal, Alberto Pérez-Cervera, Gemma Huguet, Tere M-Seara, Caroline Haimerl, David Angulo-Garcia, Alessandro Torcini, Rosa Cossart, Arnaud Malvache, Kaoutar Skiker, Mounir Maouene, Gianmarco Ragognetti, Letizia Lorusso, Andrea Viggiano, Angelo Marcelli, Rosa Senatore, Antonio Parziale, S. Stramaglia, M. Pellicoro, L. Angelini, E. Amico, H. Aerts, J. Cortés, S. Laureys, D. Marinazzo, I. Bassez, L. Faes, Hannes Almgren, Adeel Razi, Frederik Van de Steen, Ruth Krebs, Hannelore Aerts, Lida Kanari, Pawel Dlotko, Martina Scolamiero, Ran Levi, Julian Shillcock, Christiaan P.J. de Kock, Kathryn Hess, Henry Markram, Cheng Ly, Gary Marsat, Tom Gillespie, Malin Sandström, Mathew Abrams, Jeffrey S. Grethe, Maryann Martone, Robin De Gernier, Sergio Solinas, Christian Rössert, Marc Haelterman, Serge Massar, Valentina Pasquale, Vito Paolo Pastore, Sergio Martinoia, Paolo Massobrio, Cristiano Capone, Núria Tort-Colet, Maria V. Sanchez-Vives, Maurizio Mattia, Ali Almasi, Shaun L. Cloherty, David B. Grayden, Yan T. Wong, Michael R. Ibbotson, Hamish Meffin, Luke Y. Prince, Krasimira Tsaneva-Atanasova, Jack R. Mellor, Alberto Mazzoni, Manuela Rosa, Jacopo Carpaneto, Luigi M. Romito, Alberto Priori, Silvestro Micera, Rosanna Migliore, Carmen Alina Lupascu, Francesco Franchina, Luca Leonardo Bologna, Armando Romani, Sára Saray, Werner Van Geit, Szabolcs Káli, Alex Thomson, Audrey Mercer, Sigrun Lange, Joanne Falck, Eilif Muller, Felix Schürmann, Dmitrii Todorov, Robert Capps, William Barnett, Yaroslav Molkov, Federico Devalle, Diego Pazó, Ernest Montbrió, Gabriela Mochol, Habiba Azab, Benjamin Y. Hayden, Rubén Moreno-Bote, Pragathi Priyadharsini Balasubramani, Srinivasa V. Chakravarthy, Vignayanandam R. Muddapu, Medorian D. Gheorghiu, Bartul Mimica, Jonathan Withlock, Raul C. Mureșan, Jennifer L. Zick, Kelsey Schultz, Rachael K. Blackman, Matthew V. Chafee, Theoden I. Netoff, Nicholas Roberts, Vivek Nagaraj, Andrew Lamperski, Logan L. Grado, Matthew D. Johnson, David P. Darrow, Davide Lonardoni, Hayder Amin, Stefano Di Marco, Alessandro Maccione, Luca Berdondini, Thierry Nieus, Marcel Stimberg, Dan F. M. Goodman, Thomas Nowotny, Veronika Koren, Valentin Dragoi, Klaus Obermayer, Samy Castro, Mariano Fernandez, Wael El-Deredy, Kesheng Xu, Jean Paul Maidana, Patricio Orio, Weiliang Chen, Iain Hepburn, Francesco Casalegno, Adrien Devresse, Aleksandr Ovcharenko, Fernando Pereira, Fabien Delalondre, Erik De Schutter, Peter Bratby, Andrew R. Gallimore, Guido Klingbeil, Criseida Zamora, Yunliang Zang, Patrick Crotty, Eric Palmerduca, Alberto Antonietti, Claudia Casellato, Csaba Erö, Egidio D’Angelo, Marc-Oliver Gewaltig, Alessandra Pedrocchi, Ilja Bytschok, Dominik Dold, Johannes Schemmel, Karlheinz Meier, Mihai A. Petrovici, Hui-An Shen, Simone Carlo Surace, Jean-Pascal Pfister, Baptiste Lefebvre, Olivier Marre, Pierre Yger, Athanasia Papoutsi, Jiyoung Park, Ryan Ash, Stelios Smirnakis, Panayiota Poirazi, Richard A. Felix, Alexander G. Dimitrov, Christine Portfors, Silvia Daun, Tibor I. Toth, Joanna Jędrzejewska-Szmek, Nadine Kabbani, Kim T. Blackwel, Bahar Moezzi, Natalie Schaworonkow, Lukas Plogmacher, Mitchell R. Goldsworthy, Brenton Hordacre, Mark D. McDonnell, Nicolangelo Iannella, Michael C. Ridding, Jochen Triesch, Reinoud Maex, Karen Safaryan, Volker Steuber, Rongxiang Tang, Yi-Yuan Tang, Darya V. Verveyko, Alexey R. Brazhe, Andrey Yu Verisokin, Dmitry E. Postnov, Cengiz Günay, Gabriella Panuccio, Michele Giugliano, Astrid A. Prinz, Pablo Varona, Mikhail I. Rabinovich, Jack Denham, Thomas Ranner, Netta Cohen, Maria Reva, Nelson Rebola, Tekla Kirizs, Zoltan Nusser, David DiGregorio, Eirini Mavritsaki, Panos Rentzelas, Nikul H. Ukani, Adam Tomkins, Chung-Heng Yeh, Wesley Bruning, Allison L. Fenichel, Yiyin Zhou, Yu-Chi Huang, Dorian Florescu, Carlos Luna Ortiz, Paul Richmond, Chung-Chuan Lo, Daniel Coca, Ann-Shyn Chiang, Aurel A. Lazar, Jennifer L. Creaser, Congping Lin, Peter Ashwin, Jonathan T. Brown, Thomas Ridler, Daniel Levenstein, Brendon O. Watson, György Buzsáki, John Rinzel, Rodica Curtu, Anh Nguyen, Sahand Assadzadeh, Peter A. Robinson, Paula Sanz-Leon, Caroline G. Forlim, Lírio O. B. de Almeida, Reynaldo D. Pinto, Francisco B. Rodríguez, Ángel Lareo, Caroline Garcia Forlim, Aaron Montero, Thiago Mosqueiro, Ramon Huerta, Francisco B. Rodriguez, Vinicio Changoluisa, Vinícius L. Cordeiro, César C. Ceballos, Nilton L. Kamiji, Antonio C. Roque, William W. Lytton, Andrew Knox, Joshua J. C. Rosenthal, Svitlana Popovych, Liqing Liu, Bin A. Wang, Tibor I. Tóth, Christian Grefkes, Gereon R. Fink, Nils Rosjat, Abraham Perez-Trujillo, Andres Espinal, Marco A. Sotelo-Figueroa, Ivan Cruz-Aceves, Horacio Rostro-Gonzalez, Martin Zapotocky, Martina Hoskovcová, Jana Kopecká, Olga Ulmanová, Evžen Růžička, Matthias Gärtner, Sevil Duvarci, Jochen Roeper, Gaby Schneider, Stefan Albert, Katharina Schmack, Michiel Remme, Susanne Schreiber, Michele Migliore, Carmen A. Lupascu, Luca L. Bologna, Stefano M. Antonel, Jean-Denis Courcol, Sami Utku Çelikok, Eva M. Navarro-López, Neslihan Serap Şengör, Rahmi Elibol, Neslihan Serap Sengor, Mustafa Yasir Özdemir, Tianyi Li, Angelo Arleo, Denis Sheynikhovich, Akihiro Nakamura, Masanori Shimono, Youngjo Song, Sol Park, Ilhwan Choi, Jaeseung Jeong, Hee-sup Shin, Sadra Sadeh, Padraig Gleeson, R. Angus Silver, Alexandra Pierri Chatzikalymniou, Frances K. Skinner, Lazaro M. Sanchez-Rodriguez, Roberto C. Sotero, Loreen Hertäg, Owen Mackwood, Henning Sprekeler, Steffen Puhlmann, Simon N. Weber, David Higgins, Laura B. Naumann, Ramakrisnan Iyer, Stefan Mihalas, Valentina Ticcinelli, Tomislav Stankovski, Peter V. E. McClintock, Aneta Stefanovska, Predrag Janjić, Dimitar Solev, Gerald Seifert, Ljupčo Kocarev, Christian Steinhäuser, Mehrdad Salmasi, Stefan Glasauer, Martin Stemmler, Danke Zhang, Chi Zhang, Armen Stepanyants, Julia Goncharenko, Lieke Kros, Neil Davey, Chris de Zeeuw, Freek Hoebeek, Ankur Sinha, Roderick Adams, Michael Schmuker, Maria Psarrou, Maria Schilstra, Benjamin Torben-Nielsen, Christoph Metzner, Achim Schweikard, Tuomo Mäki-Marttunen, Bartosz Zurowski, Daniele Marinazzo, Luca Faes, Sebastiano Stramaglia, Henry O. C. Jordan, Simon M. Stringer, Elżbieta Gajewska-Dendek, Piotr Suffczyński, Nicoladie Tam, George Zouridakis, Luca Pollonini, Mojtaba Madadi Asl, Alireza Valizadeh, Peter A. Tass, Andreas Nold, Wei Fan, Sara Konrad, Heiko Endle, Johannes Vogt, Tatjana Tchumatchenko, Juliane Herpich, Christian Tetzlaff, Jannik Luboeinski, Timo Nachstedt, Manuel Ciba, Andreas Bahmer, Christiane Thielemann, Eric S. Kuebler, Joseph S. Tauskela, Jean-Philippe Thivierge, Rembrandt Bakker, María García-Amado, Marian Evangelio, Francisco Clascá, Paul Tiesinga, Christopher L. Buckley, Taro Toyoizumi, Alexis M. Dubreuil, Rémi Monasson, Alessandro Treves, Davide Spalla, Sophie Rosay, Florence I. Kleberg, Willy Wong, Bruno de Oliveira Floriano, Toshihiko Matsuo, Tetsuya Uchida, Domenica Dibenedetto, Kâmil Uludağ, Abdorreza Goodarzinick, Maximilian Schmidt, Claus C. Hilgetag, Markus Diesmann, Sacha J. van Albada, Michael Fauth, Mark van Rossum, Manuel Reyes-Sánchez, Rodrigo Amaducci, Carlos Muñiz, Irene Elices, David Arroyo, Rafael Levi, Ben Cohen, Carson Chow, Shashaank Vattikuti, Elena Bertolotti, Raffaella Burioni, Matteo di Volo, Alessandro Vezzani, Bayar Menzat, Tim P. Vogels, Nobuhiko Wagatsuma, Susmita Saha, Reena Kapoor, Robert Kerr, John Wagner, Luis C. Garcia del Molino, Guangyu Robert Yang, Jorge F. Mejias, Xiao-Jing Wang, Hanbing Song, Joseph Goodliffe, Jennifer Luebke, Christina M. Weaver, John Thomas, Nishant Sinha, Nikhita Shaju, Tomasz Maszczyk, Jing Jin, Sydney S. Cash, Justin Dauwels, M. Brandon Westover, Maryam Karimian, Michelle Moerel, Peter De Weerd, Thomas Burwick, Ronald L. Westra, Romesh Abeysuriya, Jonathan Hadida, Stamatios Sotiropoulos, Saad Jbabdi, Mark Woolrich, Chama Bensmail, Borys Wrobel, Xiaolong Zhou, Zilong Ji, Xiao Liu, Yan Xia, Si Wu, Xiao Wang, Mingsha Zhang, Netanel Ofer, Orit Shefi, Gur Yaari, Ted Carnevale, Amit Majumdar, Subhashini Sivagnanam, Kenneth Yoshimoto, Elena Y. Smirnova, Dmitry V. Amakhin, Sergey L. Malkin, Aleksey V. Zaitsev, Anton V. Chizhov, Margarita Zaleshina, Alexander Zaleshin, Victor J. Barranca, George Zhu, Quinton M. Skilling, Daniel Maruyama, Nicolette Ognjanovski, Sara J. Aton, Michal Zochowski, Jiaxing Wu, Sara Aton, Scott Rich, Victoria Booth, Maral Budak, Salvador Dura-Bernal, Samuel A. Neymotin, Benjamin A. Suter, Gordon M. G. Shepherd, Melvin A. Felton, Alfred B. Yu, David L. Boothe, Kelvin S. Oie, Piotr J. Franaszczuk, Sergey A. Shuvaev, Batuhan Başerdem, Anthony Zador, Alexei A. Koulakov, Víctor J. López-Madrona, Ernesto Pereda, Claudio R. Mirasso, Santiago Canals, Stefano Masoli, Udaya B. Rongala, Anton Spanne, Henrik Jorntell, Calogero M. Oddo, Alexander V. Vartanov, Anastasia K. Neklyudova, Stanislav A. Kozlovskiy, Andrey A. Kiselnikov, Julia A. Marakshina, Maria Teleńczuk, Bartosz Teleńczuk, Alain Destexhe, Paula T. Kuokkanen, Anna Kraemer, Thomas McColgan, Catherine E. Carr, and Richard Kempter

Subjects
Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571, Neurophysiology and neuropsychology, QP351-495
Published
2017
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4. High-resolution bioelectrical imaging of Aβ-induced network dysfunction on CMOS-MEAs for neurotoxicity and rescue studies

Author

Hayder Amin, Thierry Nieus, Davide Lonardoni, Alessandro Maccione, and Luca Berdondini

Subjects
Medicine, Science
Abstract

Abstract Neurotoxicity and the accumulation of extracellular amyloid-beta1–42 (Aβ) peptides are associated with the development of Alzheimer’s disease (AD) and correlate with neuronal activity and network dysfunctions, ultimately leading to cellular death. However, research on neurodegenerative diseases is hampered by the paucity of reliable readouts and experimental models to study such functional decline from an early onset and to test rescue strategies within networks at cellular resolution. To overcome this important obstacle, we demonstrate a simple yet powerful in vitro AD model based on a rat hippocampal cell culture system that exploits large-scale neuronal recordings from 4096-electrodes on CMOS-chips for electrophysiological quantifications. This model allows us to monitor network activity changes at the cellular level and to uniquely uncover the early activity-dependent deterioration induced by Aβ-neurotoxicity. We also demonstrate the potential of this in vitro model to test a plausible hypothesis underlying the Aβ-neurotoxicity and to assay potential therapeutic approaches. Specifically, by quantifying N-methyl D-aspartate (NMDA) concentration-dependent effects in comparison with low-concentration allogenic-Aβ, we confirm the role of extrasynaptic-NMDA receptors activation that may contribute to Aβ-neurotoxicity. Finally, we assess the potential rescue of neural stem cells (NSCs) and of two pharmacotherapies, memantine and saffron, for reversing Aβ-neurotoxicity and rescuing network-wide firing.

Published
2017
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5. Investigating the Effects of Mechanical Stimulation on Retinal Ganglion Cell Spontaneous Spiking Activity

Author

Marica Marrese, Davide Lonardoni, Fabio Boi, Hedde van Hoorn, Alessandro Maccione, Stefano Zordan, Davide Iannuzzi, and Luca Berdondini

Subjects
mechanical stimulation, high-density electrophysiology, retina, neural circuits, viscoelasticity, spontaneous activity, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract

Mechanical forces are increasingly recognized as major regulators of several physiological processes at both the molecular and cellular level; therefore, a deep understanding of the sensing of these forces and their conversion into electrical signals are essential for studying the mechanosensitive properties of soft biological tissues. To contribute to this field, we present a dual-purpose device able to mechanically stimulate retinal tissue and to record the spiking activity of retinal ganglion cells (RGCs). This new instrument relies on combining ferrule-top micro-indentation, which provides local measurements of viscoelasticity, with high-density multi-electrode array (HD-MEAs) to simultaneously record the spontaneous activity of the retina. In this paper, we introduce this instrument, describe its technical characteristics, and present a proof-of-concept experiment that shows how RGC spiking activity of explanted mice retinas respond to mechanical micro-stimulations of their photoreceptor layer. The data suggest that, under specific conditions of indentation, the retina perceive the mechanical stimulation as modulation of the visual input, besides the longer time-scale of activation, and the increase in spiking activity is not only localized under the indentation probe, but it propagates across the retinal tissue.

Published
2019
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6. Recurrently connected and localized neuronal communities initiate coordinated spontaneous activity in neuronal networks.

Author

Davide Lonardoni, Hayder Amin, Stefano Di Marco, Alessandro Maccione, Luca Berdondini, and Thierry Nieus

Subjects
Biology (General), QH301-705.5
Abstract

Developing neuronal systems intrinsically generate coordinated spontaneous activity that propagates by involving a large number of synchronously firing neurons. In vivo, waves of spikes transiently characterize the activity of developing brain circuits and are fundamental for activity-dependent circuit formation. In vitro, coordinated spontaneous spiking activity, or network bursts (NBs), interleaved within periods of asynchronous spikes emerge during the development of 2D and 3D neuronal cultures. Several studies have investigated this type of activity and its dynamics, but how a neuronal system generates these coordinated events remains unclear. Here, we investigate at a cellular level the generation of network bursts in spontaneously active neuronal cultures by exploiting high-resolution multielectrode array recordings and computational network modelling. Our analysis reveals that NBs are generated in specialized regions of the network (functional neuronal communities) that feature neuronal links with high cross-correlation peak values, sub-millisecond lags and that share very similar structural connectivity motifs providing recurrent interactions. We show that the particular properties of these local structures enable locally amplifying spontaneous asynchronous spikes and that this mechanism can lead to the initiation of NBs. Through the analysis of simulated and experimental data, we also show that AMPA currents drive the coordinated activity, while NMDA and GABA currents are only involved in shaping the dynamics of NBs. Overall, our results suggest that the presence of functional neuronal communities with recurrent local connections allows a neuronal system to generate spontaneous coordinated spiking activity events. As suggested by the rules used for implementing our computational model, such functional communities might naturally emerge during network development by following simple constraints on distance-based connectivity.

Published
2017
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9. From dynamics to links: a sparse reconstruction of the topology of a neural network

Author

Giacomo Aletti, Giovanni Naldi, Thierry Nieus, and Davide Lonardoni

Subjects
FOS: Computer and information sciences, 0301 basic medicine, Computer science, lasso method, Topology (electrical circuits), Topology, Statistics - Applications, Industrial and Manufacturing Engineering, 03 medical and health sciences, 0302 clinical medicine, FOS: Mathematics, Biological neural network, Applications (stat.AP), Mathematics - Numerical Analysis, T57-57.97, Applied mathematics. Quantitative methods, Quantitative Biology::Neurons and Cognition, Artificial neural network, Applied Mathematics, Information processing, Numerical Analysis (math.NA), Function (mathematics), neural networks, sparse reconstruction, Electrophysiology, Identification (information), 030104 developmental biology, FOS: Biological sciences, Quantitative Biology - Neurons and Cognition, Neurons and Cognition (q-bio.NC), Spike (software development), 030217 neurology & neurosurgery
Abstract

One major challenge in neuroscience is the identification of interrelations between signals reflecting neural activity and how information processing occurs in the neural circuits. At the cellular and molecular level, mechanisms of signal transduction have been studied intensively and a better knowledge and understanding of some basic processes of information handling by neurons has been achieved. In contrast, little is known about the organization and function of complex neuronal networks. Experimental methods are now available to simultaneously monitor electrical activity of a large number of neurons in real time. Then, the qualitative and quantitative analysis of the spiking activity of individual neurons is a very valuable tool for the study of the dynamics and architecture of the neural networks. Such activity is not due to the sole intrinsic properties of the individual neural cells but it is mostly the consequence of the direct influence of other neurons. The deduction of the effective connectivity between neurons, whose experimental spike trains are observed, is of crucial importance in neuroscience: first for the correct interpretation of the electro-physiological activity of the involved neurons and neural networks, and, for correctly relating the electrophysiological activity to the functional tasks accomplished by the network. In this work, we propose a novel method for the identification of connectivity of neural networks using recorded voltages. Our approach is based on the assumption that the network has a topology with sparse connections. After a brief description of our method, we will report the performances and compare it to the cross-correlation computed on the spike trains, which represents a gold standard method in the field.

Published
2019
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10. Constitutive Inactivation of the PRRT2 Gene Alters Short-Term Synaptic Plasticity and Promotes Network Hyperexcitability in Hippocampal Neurons

Author

Giorgia Giansante, Enrico Castroflorio, Anna Corradi, Floriana Fruscione, Caterina Michetti, Nicola Forte, Flavia Valtorta, Thierry Nieus, Anna Fassio, Pierluigi Valente, Federico Zara, Pietro Baldelli, Fabio Benfenati, Davide Lonardoni, Jin Wu Tsai, Bruno Sterlini, Alessandra Romei, Manuela Fadda, Valente, P., Romei, A., Fadda, M., Sterlini, B., Lonardoni, D., Forte, N., Fruscione, F., Castroflorio, E., Michetti, C., Giansante, G., Valtorta, F., Tsai, J. -W., Zara, F., Nieus, T., Corradi, A., Fassio, A., Baldelli, P., and Benfenati, F.

Subjects
Male, hippocampus, Cognitive Neuroscience, knockout, Hippocampus, Hippocampal formation, Biology, Neurotransmission, Inhibitory postsynaptic potential, Exocytosis, 050105 experimental psychology, Membrane Potentials, 03 medical and health sciences, Cellular and Molecular Neuroscience, 0302 clinical medicine, Neural Pathways, Animals, synaptic transmission, 0501 psychology and cognitive sciences, Cells, Cultured, Mice, Knockout, Neurons, Neuronal Plasticity, hippocampu, 05 social sciences, Membrane Proteins, Mice, Inbred C57BL, Electrophysiology, Synapses, Synaptic plasticity, Excitatory postsynaptic potential, hippocampus, knockout, network excitability, PRRT2, synaptic transmission, PRRT2, Neuroscience, network excitability, 030217 neurology & neurosurgery
Abstract

Mutations in PRoline-Rich Transmembrane protein 2 (PRRT2) underlie a group of paroxysmal disorders including epilepsy, kinesigenic dyskinesia and migraine. Most of the mutations lead to impaired PRRT2 expression and/or function, emphasizing the pathogenic role of the PRRT2 deficiency. In this work, we investigated the phenotype of primary hippocampal neurons obtained from mouse embryos in which the PRRT2 gene was constitutively inactivated. Although PRRT2 is expressed by both excitatory and inhibitory neurons, its deletion decreases the number of excitatory synapses without significantly affecting the number of inhibitory synapses or the nerve terminal ultrastructure. Analysis of synaptic function in primary PRRT2 knockout excitatory neurons by live imaging and electrophysiology showed slowdown of the kinetics of exocytosis, weakened spontaneous and evoked synaptic transmission and markedly increased facilitation. Inhibitory neurons showed strengthening of basal synaptic transmission, accompanied by faster depression. At the network level these complex synaptic effects resulted in a state of heightened spontaneous and evoked activity that was associated with increased excitability of excitatory neurons in both PRRT2 knockout primary cultures and acute hippocampal slices. The data indicate the existence of network instability/hyperexcitability as the possible basis of the paroxysmal phenotypes associated with PRRT2 mutations.

Published
2018
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11. Active High-Density Electrode Arrays: Technology and Applications in Neuronal Cell Cultures

Author

Davide, Lonardoni, Hayder, Amin, Stefano, Zordan, Fabio, Boi, Aziliz, Lecomte, Gian Nicola, Angotzi, and Luca, Berdondini

Subjects
Electrophysiology, Neurons, Cell Culture Techniques, Action Potentials, Humans, Microelectrodes
Abstract

Active high-density electrode arrays realized with complementary metal-oxide-semiconductor (CMOS) technology provide electrophysiological recordings from several thousands of closely spaced microelectrodes. This has drastically advanced the spatiotemporal recording resolution of conventional multielectrode arrays (MEAs). Thus, today's electrophysiology in neuronal cultures can exploit label-free electrical readouts from a large number of single neurons within the same network. This provides advanced capabilities to investigate the properties of self-assembling neuronal networks, to advance studies on neurotoxicity and neurodevelopmental alterations associated with human brain diseases, and to develop cell culture models for testing drug- or cell-based strategies for therapies.Here, after introducing the reader to this neurotechnology, we summarize the results of different recent studies demonstrating the potential of active high-density electrode arrays for experimental applications. We also discuss ongoing and possible future research directions that might allow for moving these platforms forward for screening applications.

Published
2019

12. Active High-Density Electrode Arrays: Technology and Applications in Neuronal Cell Cultures

Author

Luca Berdondini, Gian Nicola Angotzi, Hayder Amin, Davide Lonardoni, Aziliz Lecomte, Fabio Boi, Stefano Zordan, Chiappalone, Michela, Pasquale, Valentina, and Frega, Monica

Subjects
0301 basic medicine, methods [Electrophysiology], instrumentation [Electrophysiology], Computer science, Cell Culture Techniques, Action Potentials, High density, physiology [Neurons], Disease modelling, 03 medical and health sciences, Microelectrode, Electrophysiology, 030104 developmental biology, 0302 clinical medicine, Neurotechnology, cytology [Neurons], Electrode, Humans, pathology [Neurons], Microelectrodes, Neuroscience, 030217 neurology & neurosurgery
Abstract

Active high-density electrode arrays realized with complementary metal-oxide-semiconductor (CMOS) technology provide electrophysiological recordings from several thousands of closely spaced microelectrodes. This has drastically advanced the spatiotemporal recording resolution of conventional multielectrode arrays (MEAs). Thus, today's electrophysiology in neuronal cultures can exploit label-free electrical readouts from a large number of single neurons within the same network. This provides advanced capabilities to investigate the properties of self-assembling neuronal networks, to advance studies on neurotoxicity and neurodevelopmental alterations associated with human brain diseases, and to develop cell culture models for testing drug- or cell-based strategies for therapies.Here, after introducing the reader to this neurotechnology, we summarize the results of different recent studies demonstrating the potential of active high-density electrode arrays for experimental applications. We also discuss ongoing and possible future research directions that might allow for moving these platforms forward for screening applications.

Published
2019
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14. High-resolution bioelectrical imaging of Aβ-induced network dysfunction on CMOS-MEAs for neurotoxicity and rescue studies

Author

Luca Berdondini, Davide Lonardoni, Thierry Nieus, Alessandro Maccione, and Hayder Amin

Subjects
0301 basic medicine, N-Methylaspartate, Science, Action Potentials, Gene Expression, Hippocampus, Receptors, N-Methyl-D-Aspartate, Article, Antiparkinson Agents, Rats, Sprague-Dawley, Tissue Culture Techniques, 03 medical and health sciences, 0302 clinical medicine, Neural Stem Cells, Memantine, Lab-On-A-Chip Devices, medicine, Premovement neuronal activity, Animals, Receptor, Neurons, Multidisciplinary, Amyloid beta-Peptides, business.industry, Plant Extracts, Neurotoxicity, medicine.disease, Crocus, Embryo, Mammalian, In vitro, Neural stem cell, Peptide Fragments, Rats, Inbred F344, 3. Good health, Rats, Electrophysiology, Adult Stem Cells, 030104 developmental biology, NMDA receptor, Medicine, Female, business, Neuroscience, Microelectrodes, 030217 neurology & neurosurgery, medicine.drug
Abstract

Neurotoxicity and the accumulation of extracellular amyloid-beta1–42 (Aβ) peptides are associated with the development of Alzheimer’s disease (AD) and correlate with neuronal activity and network dysfunctions, ultimately leading to cellular death. However, research on neurodegenerative diseases is hampered by the paucity of reliable readouts and experimental models to study such functional decline from an early onset and to test rescue strategies within networks at cellular resolution. To overcome this important obstacle, we demonstrate a simple yet powerful in vitro AD model based on a rat hippocampal cell culture system that exploits large-scale neuronal recordings from 4096-electrodes on CMOS-chips for electrophysiological quantifications. This model allows us to monitor network activity changes at the cellular level and to uniquely uncover the early activity-dependent deterioration induced by Aβ-neurotoxicity. We also demonstrate the potential of this in vitro model to test a plausible hypothesis underlying the Aβ-neurotoxicity and to assay potential therapeutic approaches. Specifically, by quantifying N-methyl D-aspartate (NMDA) concentration-dependent effects in comparison with low-concentration allogenic-Aβ, we confirm the role of extrasynaptic-NMDA receptors activation that may contribute to Aβ-neurotoxicity. Finally, we assess the potential rescue of neural stem cells (NSCs) and of two pharmacotherapies, memantine and saffron, for reversing Aβ-neurotoxicity and rescuing network-wide firing.

Published
2016

15. A computational model of cell culture dynamics: the role of connectivity and synaptic receptors in the appearance of synchronized bursting events

Author

Hayder Amin, Thierry Nieus, Stefano Di Marco, Luca Berdondini, and Davide Lonardoni

Subjects
0303 health sciences, Artificial neural network, Computer science, General Neuroscience, Information processing, AMPA receptor, Network dynamics, 03 medical and health sciences, Cellular and Molecular Neuroscience, Bursting, 0302 clinical medicine, Order (biology), Poster Presentation, Neuroscience, 030217 neurology & neurosurgery, Biological network, Cultured neuronal network, 030304 developmental biology
Abstract

How an ensemble of neurons wires together to form a functional unit is a fundamental problem in neuroscience. The architecture of neuronal wiring, in fact, determines how neurons communicate and may be important for information processing performed by neuronal networks. However current knowledge is mainly limited to networks consisting of a small number of neurons, while the topological structure of biological networks remains still unknown. Primary neuronal cultures represent an ideal preparation to investigate the basic principles of network dynamics. At the mature stage, they display network-wide synchronous bursting events (SBEs) sharing similar spatiotemporal patterns of firing [1]. Interestingly, high-density MEA recordings have shown that SBEs actually correspond to propagating activities through the network. Typically, the simulated SBEs originated from a few and specific sites as in experiments [2], but the nature and the role of such events is still under debate. In order to investigate the determinants of such dynamics, we developed a computational model that mimics the main features of the recordings obtained by a high density multi-electrode-array device (4096 electrodes inter-spaced by 20um, [3]). With only a few topological constraints, the model expressed realistic SBEs along time that can be well clustered into only a few groups differing for their ignition sites and propagation directions, similarly to what it is observed experimentally. Furthermore, we used the model together with experimental datasets to investigate the effects of synaptic blockers of the AMPA, NMDA and GABA synapses on the network activity. In particular, we showed that NMDA receptors can be among the principal mechanisms involved in triggering a sequence of SBEs, a firing regime that is typically observed in for mature neuronal cultures. Such regime is characterized by a principal SBE recruiting a great percentage of neurons and followed by a sequence of several weaker SBEs interleaved by hundreds of milliseconds. Altogether, the results obtained with our neural network computational model show that this model can replicate most of the salient firing properties observed experimentally in cultured neuronal networks and that it can serve for exploring the properties of signals and responses observed in neuronal networks properties.

Published
2015
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16. High-density MEA recordings unveil the dynamics of bursting events in Cell Cultures

Author

Alessandro Maccione, Hayder Amin, Thierry Nieus, Luca Berdondini, Stefano Di Marco, and Davide Lonardoni

Subjects
Cells, Cell Culture Techniques, Biomedical Engineering, Action Potentials, High density, Health Informatics, Biology, Hippocampus, Bursting, Biological neural network, Electrode array, Animals, Collective dynamics, Cells, Cultured, Neurons, Cultured, Microelectrodes, Nerve Net, Rats, Signal Processing, 1707, food and beverages, Microelectrode, Electrode, Neuroscience, Biomedical engineering
Abstract

High density multielectrode arrays (MEAs) based on CMOS technology (CMOS-MEAs) can simultaneously record extracellular spiking activity in neuronal cultures from 4096 closely spaced microelectrodes. This allows for a finer investigation of neuronal network activity compared to conventional MEAs with a few tens of electrodes. However, the sensing properties of these devices differ. To highlight this aspect, here we investigate and discuss the differences observed when quantifying spontaneous synchronized bursting events (SBEs) in datasets acquired with conventional MEAs and high-density MEAs from comparable hippocampal cultures. We found that datasets acquired with high-density MEAs exhibit collective dynamics similar to conventional arrays, but are characterized by a higher percentage of random spikes, i.e. spikes that are not part of a burst, most probably resulting from the larger recording capability. Additionally, the percentage of electrodes that record a burst is remarkably small on high-density MEAs compared to what can be observed on conventional MEAs and SBEs appear to be propagating in time across the electrode array, by involving shorter sequences of spikes per electrode. Overall, these results highlight a lower level of network synchronization involved in SBEs compared to what has been debated for several decades based on conventional MEA recordings from cell cultures.

Published
2015
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17. From 2D to 3D: novel nanostructured scaffolds to investigate signalling in reconstructed neuronal networks

Author

Antonio Turco, Maurizio Prato, Jummi Laishram, Davide Lonardoni, Thierry Nieus, Susanna Bosi, Rossana Rauti, Denis Scaini, Laura Ballerini, Bosi, Susanna, Rauti, Rossana, Laishram, Jummi, Turco, Antonio, Lonardoni, Davide, Nieus, Thierry, Prato, Maurizio, Scaini, Deni, and Ballerini, Laura

Subjects
nanomaterials, scaffolds, tissue engineering, synaptic networks, carbon nanotubes, Computer science, Cell, Cell Culture Techniques, Nanotechnology, Carbon nanotube, scaffold, Settore BIO/09 - Fisiologia, Article, law.invention, Nanomaterials, Tissue culture, Tissue engineering, law, medicine, Animals, Calcium Signaling, Dimethylpolysiloxanes, Cells, Cultured, Neurons, Microscopy, Confocal, Multidisciplinary, Tissue Scaffolds, Nanotubes, Carbon, Models, Theoretical, Network dynamics, Nanostructures, Rats, medicine.anatomical_structure, Signalling, Neuronal circuits, synaptic network, nanomaterial, Porosity
Abstract

To recreate in vitro 3D neuronal circuits will ultimately increase the relevance of results from cultured to whole-brain networks and will promote enabling technologies for neuro-engineering applications. Here we fabricate novel elastomeric scaffolds able to instruct 3D growth of living primary neurons. Such systems allow investigating the emerging activity, in terms of calcium signals, of small clusters of neurons as a function of the interplay between the 2D or 3D architectures and network dynamics. We report the ability of 3D geometry to improve functional organization and synchronization in small neuronal assemblies. We propose a mathematical modelling of network dynamics that supports such a result. Entrapping carbon nanotubes in the scaffolds remarkably boosted synaptic activity, thus allowing for the first time to exploit nanomaterial/cell interfacing in 3D growth support. Our 3D system represents a simple and reliable construct, able to improve the complexity of current tissue culture models.

Published
2015

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