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Item 25th Annual Computational Neuroscience Meeting: CNS-2016(BioMed Central, 2016-08-18) Sharpee, Tatyana O.; Destexhe, Alain; Kawato, Mitsuo; Sekulić, Vladisla; Skinner, Frances K.; Wójcik, Daniel K.; Chintaluri, Chaitanya; Cserpán, Dorottya; Somogyvári, Zoltán; Kim, Jae Kyoung; Kilpatrick, Zachary P.; Bennett, Matthew R.; Josić, Kresimir; Elices, Irene; Arroyo, David; Levi, Rafael; Rodriguez, Francisco B.; Varona, Pablo; Hwang, Eunjin; Kim, Bowon; Han, Hio-Been; Kim, Tae; McKenna, James T.; Brown, Ritchie E.; McCarley, Robert W.; Choi, Jee Hyun; Rankin, James; Popp, Pamela Osborn; Rinzel, John; Tabas, Alejandro; Rupp, André; Balaguer‑Ballester, Emili; Maturana, Matias I.; Grayden, David B.; Cloherty, Shaun L.; Kameneva, Tatiana; Ibbotson, Michael R.; Meffin, Hamish; Koren, Veronika; Lochmann, Timm; Dragoi, Valentin; Obermayer, Klaus; Psarrou, Maria; Schilstra, Maria; Davey, Neil; Ju, Huiwen; Hines, Michael L.; Chen, Liang; Kim, Jimin; Leahy, Will; Shlizerman, Eli; Birgolias, Justas; Gerkin, Richard C.; Crook, Sharon M.; Viriyopase, Atthaphon; Memmeshei, Raol-Martin; Dabaghian, Yuri; DeVuti, Justin; Perotti, Luca; Kim, Ammo J.; Fenk, Lisa M.; Lyu, Cheng; Malmon, Gabby; Zhao, Chang; Widmer, Yves; Sprecher, Simon; Halnes, Geir; Tuomo, Maki-Martun; Keller, Daniel; Petterson, Klas H.; Andreassen, Ole A.; Elnevoll, Gaute T.; Yamada, Yasnori; Steyn-Ross, Moira L.; Steyn-Ross, D. Alistair; Meijas, Jorge F.; Murray, John D.; Kennedy, Henry; Kruscha, Alexandra; Grewe, Jan; Lidner, Benjamin; Badel, Laurent; Kasumi, Ohta; Tsuchimoto, Yoshiko; Kazama, Hokto; Kahng, B.; Tam, Nicoladie D.; Pollonini, Luca; Zouridakis, George; Soh, Jaehyun; Kim, DaeEun; Yoo, Minsu; Palmer, S.E.; Culmone, Viviana; Bojak, Ingo; Ferrario, Andrea; Merriosn-Hort, Robert; Borisyuk, Roman; Kim, Chang Sub; Tezuka, Taro; Joo, Pangyu; Young-Ah, Rho; Burton, Shawn D.; Bard, G.; Marsalek, Petr; Kim, Hoon-Hee; Moon, Seok-hun; Lee, Do-won; Molkov, Yaroslav I.; Hamade, Khaldoun; Teka, Wondimu; Barnett, William H.; Kim, Taegyo; Markin, Sergey; Rybak, Ilya A.; Forrow, Csaba; Demutz, Harald; Demkó, László; Vörös, János; Dabaghian, Yuri; Babichev, Andrey; Huang, Haiping; Metzner, Christoph; Schwikard, Achim; Zurowski, Bartosz; Roach, James P.; Sander, Leonard M.; Zochowski, Michal R.; Skilling, Quinton M.; Ognjanovski, Nicolette; Aton, Sara J.; Zochowski, Michal; Wang, Sheng-Ju; Ouyang, Guang; Zhang, Mingsha; Wong, Michael; Zhou, Changsong; Robinson, Peter A.; Sanz-Leon, Paula; Drysdale, Peter M.; Fung, Felix; Abeysuriya, Romesh G.; Rennle, Chris J.; Zhao, Xuelong; Choe, Yoonsuck; Yang, Huei-Fang; Mi, Yuanyuan; Lin, Xiahoan; Wu, Si; Liedtke, Joscha; Schottdorf, Manual; Wolf, Fred; Yamamura, Yorkio; Wickens, Jeffery R.; Rumbell, Timothy; Ramsey, Julia; Reyes, Amy; Draguljić, Daniel; Hof, Patrick R.; Luebke, Jennifer; Weaver, Christina M.; He, Hu; Yang, Xu; Ma, Hailin; Xu, Zhiheng; Wang, Yuzhe; Baek, Kwangyeol; Morris, Laurel S.; Kundu, Prantik; Voon, Valerie; Agnes, Everton J.; Vogels, Tim P.; Giese, Martin; Kuravi, Pradeep; Vogels, Rufin; Seeholzer, Alexander; Podlaski, William; Ranjan, Rajnish; Vogels, Tim; Torres, Joaquin J.; Baroni, Fabiano; Latorre, Roberto; Varona, Pablo; Gips, Bart; Lowet, Eric; Roberts, Mark J.; de Weerd, Peter; Jensen, Ole; van der Eerden, Jan; Goodarzinic, Abdorreza; Niry, Mohammad; Valizadeh, Alireza; Pariz, Aref; Parsi, Shervin S.; Valizadeh, Alireza; Warburton, Julia M.; Marucci, Lucia; Tamagnini, Francesco; Brown, John; Tsaneva‑Atanasova, Krasimira; Kleberg, Florence I.; Triesch, Jochen; Moezzi, Bahar; Iannella, Nicolangelo; Schaworonkow, Natalie; Plogmacher, Lukas; Goldsworthy, Mitchell R.; Hordacre, Brenton; McDonnell, Mark D.; Ridding, Michael C.; Trisch, Jochen; Zaptocky, Martin; Smit, Daniel; Fouquet, Coralie; Trembleau, Alain; Dasgupta, Sakyasingha; Nishikawa, Isao; Aihara, Kazuyuki; Toyoizumi, Taro; Robb, Daniel T.; Mellen, Nick; Toporikova, Natalia; Tang, Rongxiang; Tang, Yi-Yuan; Kiser, Seth A.; Howard Jr., James H.; Tang, Yi-Yuan; Goncharenko, Julia; Davey, Neil; Schilstra, Marla; Steuber, Volker; Voronenko, Sergej O.; Linder, Benjamin; Ahamed, Tosif; Stephens, Greg; Yger, Pierre; Lefebvre, Baptiste; Spampinato, Giulia Lia Beatrice; Esposito, Elric; Stimberg, Marcel; Marre, Olivier; Choi, Hansol; Song, Min-Ho; Chung, SueYeon; Lee, Dan D.; Sompolinsky, Haim; Phillips, Ryan S.; Smith, Jeffrey; Chatzikalymniou, Alexandra Pierri; Ferguson, Katie; Skinner, Frances K.; Gajic, N. Alex Cayco; Clopath, Claudia; Silver, R. Angus; Gleeson, Padraig; Marin, Boris; Sadeh, Sadra; Quintana, Adrian; Cantarelli, Matteo; Dura‑Bernal, Salvador; Lytton, William W.; Davison, Andrew; Silver, Angus; Li, Luozheng; Zhang, Wenhao; Mi, Yuanyuan; Wang, Dahui; Wu, Sl; Song, Youngjo; Park, Sol; Choi, Ilhwan; Jeong, Jaeseung; Shin, Hee‑sup; Choi, Hannah; Pasupathy, Anitha; Shea-Brown, Eric; Huh, Dongsung; Sejnowski, Terrence J.; Vogt, Simon M.; Kumar, Arvind; Schmidt, Robert; Werdt, Stephen Van; Schiff, Steven J.; Veale, Richard; Scheutz, Matthias; Lee, Sang Wan; Gallinaro, Júlia; Rotter, Stefan; Sanz‑Leon, Paula; Robinson, Peter A.; Rubchinsky, Leonid L.; Cheung, Chung Ching; Ratnadurai‑Giridharan, Shivakeshavan; Shomali, Safura Rashid; Ahmadabadi, Majid Nili; Shimazaki, Hideaki; Rasuli, Nader; Zhao, Xiaochen; Rasch, Malte J.; Witting, Jens; Priesemann, Viola; Levina, Anna; Priesemann, Viola; Lizler, Joseph T.; Spinney, Richard E.; Rubinov, Mikail; Wibral, Michael; Bak, Ji Hyun; Pillow, Jonathan; Zaho, Yuan; Park, Memming; Kang, Jiyoung; Park, Hae‑Jeong; Jang, Jaeson; Paik, Se-Bum; Choi, Woochul; Lee, Changju; Jang, Jaeson; Paik, Se‑Bum; Song, Min; Lee, Hyeonsu; Yilmaz, Ergin; Baysal, Velt; Ozer, Mahmut; Koren, Veronika; Obermayer, Klaus; Saska, Daniel; Nowotny, Thomas; Chan, Ho Ka; Diamond, Alan; Hermann, Christoph S.; Murray, Micha M.; Ionta, Silvlo; Hutt, Axel; Lefebvre, Jérémie; Weidel, Philipp; Duarte, Renato; Morrison, Abigail; Iyer, Ramakrishnan; Mihalas, Stefan; Petrovici, Mihai A.; Leng, Luziwei; Breitwieser, Oliver; Stöckel, David; Bytschok, Ilja; Martel, Roman; Bill, Johannes; Schemmel, Johannes; Meier, Karlheinz; Esler, Timothy B.; Burkitt, Anthony N.; Grayden, David B.; Kerr, Robert R.; Tahayori, Bahman; Meffin, Hamish; Moezzi, Bahar; Iannella, Nicolangelo; McDonnell, Mark D.; Nolte, Max; Reimann, Michael W.; Muler, Eilif; Markram, Henry; Parziale, Antonio; Senatore, Rosa; Marcelli, Angelo; Maouene, M.; Skiker, K.; Neymotin, Samuel A.; Dura‑Bernal, Salvador; Seidenstein, Alexandra; Lakatos, Peter; Sanger, Terence D.; Lytton, William W.; Dura‑Bernal, Salvador; Menzies, Rosemary J.; McLauchlan, Campbell; van Albada, Sacha J.; Kedziora, David J.; Neymotin, Samuel; Kerr, Cliff C.; Ryu, Juhyoung; Lee, Sang-Hun; Lee, Joonwon; Lee, Hyang Jung; Lim, Daeseob; Lee, Jung H.; Wang, Jisung; Lee, Heonsoo; Jung, Nam; Quang, Le Anh; Maeng, Seung Eu; Lee, Tae Ho; Lee, Jae Woo; Park, Chang-hyun; Ahn, Sora; Moon, Jangsup; Choi, Yun Seo; Kim, Juhee; Jun, Sang Beom; Lee, Seungjun; Lee, Hyang Woon; Jo, Sumin; Jun, Eunji; Yu, Suin; Goetze, Felix; Lai, Pik‑Yin; Kwag, Jeehyun; Liang, Guangsheng; Jang, Hyun Jae; Filipovi, Marko; Reig, Ramon; Aertsen, Ad; Silberberg, Gilad; Kumar, Arvind; Bachmann, Claudia; Buttler, Simone; Jacobs, Heidi; Dillen, Kim; Fink, Gereon R.; Kukolja, Juraj; Kepple, Daniel; Giaffar, Hamza; Rinberg, Dima; Shea, Steven; Koulakov, Alex; Bahuguna, Jyotika; Tetzlaff, Tom; Kotaleski, Jeanette Hellgren; Kunze, Tim; Peterson, Andre; Knösche, Thomas; Kim, Minjung; Kim, Hojeong; Park, Ji Sung; Yeon, Ji Won; Kim, Sung-Phil; Lee, Chungho; Kim, Sung-Phil; Spiegler, Andreas; Petkoski, Spase; Palva, Matias J.; Jirsa, Viktor K.; Saggio, Maria L.; Siep, Silvan F.; Stacey, William C.; Bernard, Christophe; Choung, Oh‑hyeon; Jeong, Yong; Lee, Yong‑il; Jeong, Jaesung; Kim, Su Hyun; Lee, Jeungmin; Kwon, Jaehyung; Kralik, Jerald D.; Hwang, Dong‑Uk; Park, Sang-Min; Kim, Seongkyun; Kim, Hyoungkyu; Lim, Sewoong; Yoon, Sangsup; Park, Choongseok; Miller, Thomas; Clements, Katie; Hye Jr., Eoon; Issa, Fadi A.; Baek, JeongHun; Oba, Shigeyuki; Yoshimoto, Junichiro; Doya, Kenji; Ishii, Shin; Mosqueiro, Thiago S; Strube‑Bloss, Martin F.; Smith, Brian; Huerta, Ramon; Hadrava, Michal; Hlinka, Jaroslav; Bos, Hannah; Helias, Moritz; Welzig, Charles M.; Harper, Zachary J.; Kim, Won Sup; Shin, In-Seob; Baek, Hyeon-Man; Han, Seung Kee; Richter, René; Vitay, Julien; Beuth, Frederick; Hamker, Fred H.; Kameneva, Tatiana; Graham, Bruce P.; Kale, Penelope J.; Gollo, Leonardo L.; Stern, Merav; Abbott, L.F.; Fedorov, Leonid A.; Giese, Martin A.; Ardestani, Mohammad Hovaidi; Giese, Martin; Chakravarthy, V.Srinivasa; Chhabria, Karishma; Philips, Ryan T.; Ardestani, Mohammad Hovaidi; Faraji, Mohammad Java; Preuschoff, Kerstin; Gerstner, Wulfram; Briaire`, Jeroen J.; Kalkman, Randy K.; Frijns, Johan H. M.; Lee, Won Hee; Frangou, Sophia; Fulcher, Ben D.; Tran, Patricia H. P.; Fornito, Alex; Gliske, Stephen V.; Stacey, William C.; Holman, Katherine A.; Fink, Christian G.; Kim, Jinseop; Mu, Shang; Briggman, Kevin L; Seung, H. Sebastian; Wegener, Detlef; Bohnenkamp, Lisa; Ernst, Udo A.; Mäki‑Marttunen, Tuomo; Halnes, Geir; Devor, Anna; Dale, Anders M.; Andreassen, Ole A.; Einevoll, Gaute T.; Hagen, Espen; Lines, Glenn T.; Edwards, Andy; Tveito, Aslak; Senk, Johanna; van Albada, Sacha J; Diesmann, Markus; Schmidt, Maximilian; Bakker, Rembrandt; Shen, Kelly; Bezgin`, Gleb; Hilgetag`, Claus‑Christian; Sun, Haoqi; Sourina, Olga; Huang, Guang-Bin; Klanner, Felix; Denk, Cornelia; Glomb, Katharina; Ponce‑Alvarez, Adrián; Gilson, Matthieu; Ritter, Petra; Deco, Gustavo; Witek, Maria A. G.; Clarke, Eric F.; Hansen, Mads; Wallentin, Mikkel; Kringelbach, Morten L.; Vuust, Peter; Klingbeil, Guido; Schutter, Erik De; Chen, Weiliang; Hong, Sungho; Takashima, Akira; Zamora, Criseida; Gallimore, Andrew R.; Karoly, Philippa J.; Freestone, Dean R.; Soundry, Daniel; Kuhlmann, Levin; Paninski, Liam; Cook, Mark; Lee, Jaejin; Fishman, Yonatan I.; Cohen, Yale E.; Cocchi, Luca; Sweeney, Yann; Lee, Soohyun; Jung, Woo-Sung; Kim, Bowon; Kim, Youngsoo; Jung, Younginha; Rankin, James; Chavane, Frédéric; Soman, Karthik; Muralidharan, Vignesh; Shivkumar, Sabyasach; Mandall, Alekhya; Priyadharsini, B. Praga; Mehta, Hima; Brinkman, Braden A.; Kekona, Tyler; Rieke, Fred; Shea‑Brown, Eric; Buice, Michael; Pittà, Maurizio De; Berry, Hugues; Brunel, Nicolas; Breakspear, Michael; Marsat, Gary; Drew, Jordan; Chapman, Phillip D.; Daly, Kevin C.; Bradley, Samual P.; Seo, Sat Byul; Su, Jianzhong; Kavalali, Enge T.; Blackwell, Justin; Shiau, LieJune; Buhry, Laure; Basnayake, Kanishka; Lee, Sue-Hyun; Levy, Brandon A.; Baker, Chris I.; Leleu, Timothée; Aihara, Kazuyuki; Department of Mathematical Sciences, School of ScienceItem Chemoreception and neuroplasticity in respiratory circuits(Elsevier, 2017-01) Barnett, William H.; Abdala, Ana P.; Paton, Julian F. R.; Rybak, Ilya A.; Zoccal, Daniel B.; Molkov, Yaroslav I.; Mathematical Sciences, School of ScienceThe respiratory central pattern generator must respond to chemosensory cues to maintain oxygen (O2) and carbon dioxide (CO2) homeostasis in the blood and tissues. To do this, sensorial cells located in the periphery and central nervous system monitor the arterial partial pressure of O2 and CO2 and initiate respiratory and autonomic reflex adjustments in conditions of hypoxia and hypercapnia. In conditions of chronic intermittent hypoxia (CIH), repeated peripheral chemoreceptor input mediated by the nucleus of the solitary tract induces plastic changes in respiratory circuits that alter baseline respiratory and sympathetic motor outputs and result in chemoreflex sensitization, active expiration, and arterial hypertension. Herein, we explored the hypothesis that the CIH-induced neuroplasticity primarily consists of increased excitability of pre-inspiratory/inspiratory neurons in the pre-Bötzinger complex. To evaluate this hypothesis and elucidate neural mechanisms for the emergence of active expiration and sympathetic overactivity in CIH-treated animals, we extended a previously developed computational model of the brainstem respiratory-sympathetic network to reproduce experimental data on peripheral and central chemoreflexes post-CIH. The model incorporated neuronal connections between the 2nd-order NTS neurons and peripheral chemoreceptors afferents, the respiratory pattern generator, and sympathetic neurons in the rostral ventrolateral medulla in order to capture key features of sympathetic and respiratory responses to peripheral chemoreflex stimulation. Our model identifies the potential neuronal groups recruited during peripheral chemoreflex stimulation that may be required for the development of inspiratory, expiratory and sympathetic reflex responses. Moreover, our model predicts that pre-inspiratory neurons in the pre-Bötzinger complex experience plasticity of channel expression due to excessive excitation during peripheral chemoreflex. Simulations also show that, due to positive interactions between pre-inspiratory neurons in the pre-Bötzinger complex and expiratory neurons in the retrotrapezoid nucleus, increased excitability of the former may lead to the emergence of the active expiratory pattern at normal CO2 levels found after CIH exposure. We conclude that neuronal type specific neuroplasticity in the pre-Bötzinger complex induced by repetitive episodes of peripheral chemoreceptor activation by hypoxia may contribute to the development of sympathetic over-activity and hypertension.Item Mechanisms of Left-Right Coordination in Mammalian Locomotor Pattern Generation Circuits: A Mathematical Modeling View(PLoS, 2015-05) Molkov, Yaroslav I.; Bacak, Bartholomew J.; Talpalar, Adolfo E.; Rybak, Ilya A.; Department of Mathematical Sciences, School of ScienceThe locomotor gait in limbed animals is defined by the left-right leg coordination and locomotor speed. Coordination between left and right neural activities in the spinal cord controlling left and right legs is provided by commissural interneurons (CINs). Several CIN types have been genetically identified, including the excitatory V3 and excitatory and inhibitory V0 types. Recent studies demonstrated that genetic elimination of all V0 CINs caused switching from a normal left-right alternating activity to a left-right synchronized “hopping” pattern. Furthermore, ablation of only the inhibitory V0 CINs (V0D subtype) resulted in a lack of left-right alternation at low locomotor frequencies and retaining this alternation at high frequencies, whereas selective ablation of the excitatory V0 neurons (V0V subtype) maintained the left–right alternation at low frequencies and switched to a hopping pattern at high frequencies. To analyze these findings, we developed a simplified mathematical model of neural circuits consisting of four pacemaker neurons representing left and right, flexor and extensor rhythm-generating centers interacting via commissural pathways representing V3, V0D, and V0V CINs. The locomotor frequency was controlled by a parameter defining the excitation of neurons and commissural pathways mimicking the effects of N-methyl-D-aspartate on locomotor frequency in isolated rodent spinal cord preparations. The model demonstrated a typical left-right alternating pattern under control conditions, switching to a hopping activity at any frequency after removing both V0 connections, a synchronized pattern at low frequencies with alternation at high frequencies after removing only V0D connections, and an alternating pattern at low frequencies with hopping at high frequencies after removing only V0V connections. We used bifurcation theory and fast-slow decomposition methods to analyze network behavior in the above regimes and transitions between them. The model reproduced, and suggested explanation for, a series of experimental phenomena and generated predictions available for experimental testing.