Sex Differences in Cancer Cachexia and a Novel Mitochondrial Target for Cancer-Induced Muscle Wasting

Cancer cachexia (CC) is a devastating wasting syndrome characterized by marked weight loss including skeletal muscle atrophy that affects approximately 80% of cancer patients. Current therapeutic treatments including pharmacological and nutritional intervention are insufficient to prevent or reverse it. Prior studies demonstrated lower muscle mass, impaired muscle function, and mitochondrial health in the development of CC. Specifically, mitochondrial fusion protein, Optic atrophy 1 (OPA1) which plays a significant role in skeletal muscle health, is suppressed in the development of CC. Furthermore, most pre-clinical CC studies were mainly focused on males although there are distinct phenotypical differences in skeletal muscle between males and females. Therefore, these studies were set to investigate two independent research questions (Chapter 3 & 4). The purpose of this dissertation project was to investigate skeletal muscle alterations during the development of CC in female tumor-bearing mice (Chapter 3) and determine the efficacy of OPA1 as a therapeutic target for cancer-induced muscle atrophy (Chapter 4). To accomplish this research plan, I completed a series of studies using both cell culture and animal models of CC. For the Chapter 3 experiments, 60 female mice were given either an IP injection of PBS or Lewis Lung Carcinoma (LLC) injection and the tumors were allowed to grow for 1, 2, 3, or 4-wk to assess the time course of cachectic development. We found a dichotomous effect on tumor mass between 3- and 4-wk animals where approximately half of mice between the two groups exhibited low tumor (LT) mass (\u3c1.2 g) while the other half developed higher tumor (HT) mass (\u3e2 g). Furthermore, HT mice revealed greater protein degradation, impaired muscle contractility, and mitochondrial degeneration. These alterations are relatively modest when compared to male data from previous studies. For the Chapter 4 experiments, I utilized both pharmacological (in vitro & in vivo) and genetic overexpression of OPA1 (OPA1 TG) in LLC-conditioned media (LCM) and LLC-induced CC. 72 hours of LCM intervention induced smaller myotubes, which was normalized by BGP-15 treatment and this effect appeared to be driven by suppressed inflammatory cytokine and autophagic-lysosomal pathway (ALP) activity at the mRNA level. 4-wk of LLC implantation was sufficient to induce cachectic phenotype while this effect was normalized in OPA1 overexpression in tumor-bearing mice. In conclusion, my dissertation data suggests both biological sex as an important variable and OPA1 as a novel therapeutic target for cancer-induced muscle wasting

Males, but Not Females, Demonstrate Mitochondrial Dysfunction in the C26 Model of Cancer Cachexia

Cancer cachexia is characterized by progressive muscle wasting that can lead to symptoms such as anemia, severe weight loss, and fatigue. These symptoms can lead to limitations in activities of daily living and can cause resistance to chemotherapy treatments in cancer patients. There are no current treatments available to treat cancer cachexia and a critical need remains to identify mechanisms of cancer cachexia. Recently, our group identified mitochondrial disfunction precedes muscle atrophy in males but not females in a model of lung cancer induced atrophy. However, it is unknown whether this finding is replicated when studying a different type of cancer. PURPOSE: This study set out to determine if mitochondrial respiration is impaired in the plantaris muscle in a well-established colon cancer model of cachexia. METHODS: The time-course study consisted of male and female mice in four groups per sex: An age-matched control (PBS), and three groups implanted with C26 tumors. Tumor growth for 10-15 days, 20 days, and 25 days. Tumors were implanted bilaterally into the hind flank for a total of 1X106 cells PBS (one-half per each hindflank). The plantaris was weighed for wet mass then teased into small fiber bundles and permeabilized for the quantification of mitochondrial function. Mitochondrial dysfunction was classified by a decrease in the respiratory control ratio (RCR), which is the ratio of state 3 (maximal ADP stimulated respiration) to state 4 (oligomycin-induced leak respiration). Male and Female data were analyzed separately using a one-way ANOVA. RESULTS: The tumor burden increased as the number of days increased. Male RCR showed a mean difference in RCR at the early timepoint (10-15 day, p=0.058) and demonstrated significantly lower RCR at the 20 day timepoint compared to PBS control (20d= 1.170± 0.094, PBS= 2.41 ± 0.13, p=0.031). Interestingly, RCR was not significantly different between male PBS and 25 days (1.864± 0.21, p=0.084). RCR in the plantaris from females was not different among any of the groups (p=0.401). CONCLUSION: Along with our previously published data in a lung cancer model, these data indicate that the mechanisms of muscle atrophy are sex dependent. Specifically, mitochondrial dysfunction appears to play an important role in cancer-induced atrophy in male, but not female, mice

Multi-transcriptome analysis following an acute skeletal muscle growth stimulus yields tools for discerning global and MYC regulatory networks

Myc is a powerful transcription factor implicated in epigenetic reprogramming, cellular plasticity, and rapid growth as well as tumorigenesis. Cancer in skeletal muscle is extremely rare despite marked and sustained Myc induction during loading-induced hypertrophy. Here, we investigated global, actively transcribed, stable, and myonucleus-specific transcriptomes following an acute hypertrophic stimulus in mouse plantaris. With these datasets, we define global and Myc-specific dynamics at the onset of mechanical overload-induced muscle fiber growth. Data collation across analyses reveals an under-appreciated role for the muscle fiber in extracellular matrix remodeling during adaptation, along with the contribution of mRNA stability to epigenetic-related transcript levels in muscle. We also identify Runx1 and Ankrd1 (Marp1) as abundant myonucleus-enriched loading-induced genes. We observed that a strong induction of cell cycle regulators including Myc occurs with mechanical overload in myonuclei. Additionally, in vivo Myc-controlled gene expression in the plantaris was defined using a genetic muscle fiber-specific doxycycline-inducible Myc-overexpression model. We determined Myc is implicated in numerous aspects of gene expression during early-phase muscle fiber growth. Specifically, brief induction of Myc protein in muscle represses Reverbα, Reverbβ, and Myh2 while increasing Rpl3, recapitulating gene expression in myonuclei during acute overload. Experimental, comparative, and in silico analyses place Myc at the center of a stable and actively transcribed, loading-responsive, muscle fiber–localized regulatory hub. Collectively, our experiments are a roadmap for understanding global and Myc-mediated transcriptional networks that regulate rapid remodeling in postmitotic cells. We provide open webtools for exploring the five RNA-seq datasets as a resource to the field

Female mice may have exacerbated catabolic signalling response compared to male mice during development and progression of disuse atrophy

Background: Muscle atrophy is a common pathology associated with disuse, such as prolonged bed rest or spaceflight, and is associated with detrimental health outcomes. There is emerging evidence that disuse atrophy may differentially affect males and females. Cellular mechanisms contributing to the development and progression of disuse remain elusive, particularly protein turnover cascades. The purpose of this study was to investigate the initial development and progression of disuse muscle atrophy in male and female mice using the well-established model of hindlimb unloading (HU). Methods: One hundred C57BL/6J mice (50 male and 50 female) were hindlimb suspended for 0 (control), 24, 48, 72, or 168 h to induce disuse atrophy (10 animals per group). At designated time points, animals were euthanized, and tissues (extensor digitorum longus, gastrocnemius, and soleus for mRNA analysis, gastrocnemius and extensor digitorum longus for protein synthesis rates, and tibialis anterior for histology) were collected for analysis of protein turnover mechanisms (protein anabolism and catabolism). Results: Both males and females lost ~30% of tibialis anterior cross-sectional area after 168 h of disuse. Males had no statistical difference in MHCIIB fibre area, whereas unloaded females had ~33% lower MHCIIB cross-sectional area by 168 h of unloading. Both males and females had lower fractional protein synthesis rates (FSRs) within 24-48 h of HU, and females appeared to have a greater reduction compared with males within 24 h of HU (~23% lower FSRs in males vs. 40% lower FSRs in females). Males and females exhibited differential patterns and responses in multiple markers of protein anabolism, catabolism, and myogenic capacity during the development and progression of disuse atrophy. Specifically, females had greater mRNA inductions of catabolic factors Ubc and Gadd45a (~4-fold greater content in females compared with ~2-fold greater content in males) and greater inductions of anabolic inhibitors Redd1 and Deptor with disuse across multiple muscle tissues exhibiting different fibre phenotypes. Conclusions: These results suggest that the aetiology of disuse muscle atrophy is more complicated and nuanced than previously thought, with different responses based on muscle phenotypes and between males and females, with females having greater inductions of atrophic markers early in the development of disuse atrophy

25th annual computational neuroscience meeting: CNS-2016

The same neuron may play different functional roles in the neural circuits to which it belongs. For example, neurons in the Tritonia pedal ganglia may participate in variable phases of the swim motor rhythms [1]. While such neuronal functional variability is likely to play a major role the delivery of the functionality of neural systems, it is difficult to study it in most nervous systems. We work on the pyloric rhythm network of the crustacean stomatogastric ganglion (STG) [2]. Typically network models of the STG treat neurons of the same functional type as a single model neuron (e.g. PD neurons), assuming the same conductance parameters for these neurons and implying their synchronous firing [3, 4]. However, simultaneous recording of PD neurons shows differences between the timings of spikes of these neurons. This may indicate functional variability of these neurons. Here we modelled separately the two PD neurons of the STG in a multi-neuron model of the pyloric network. Our neuron models comply with known correlations between conductance parameters of ionic currents. Our results reproduce the experimental finding of increasing spike time distance between spikes originating from the two model PD neurons during their synchronised burst phase. The PD neuron with the larger calcium conductance generates its spikes before the other PD neuron. Larger potassium conductance values in the follower neuron imply longer delays between spikes, see Fig. 17.Neuromodulators change the conductance parameters of neurons and maintain the ratios of these parameters [5]. Our results show that such changes may shift the individual contribution of two PD neurons to the PD-phase of the pyloric rhythm altering their functionality within this rhythm. Our work paves the way towards an accessible experimental and computational framework for the analysis of the mechanisms and impact of functional variability of neurons within the neural circuits to which they belong

ENHANCED INSULIN SIGNALING FOLLOWING CONTRACTILE ACTIVITY IS BLUNTED IN MYOTUBES FROM SEVERELY OBESE INDIVIDUALS WITH OR WITHOUT TYPE 2 DIABETES

Introduction: Regular exercise has been known to improve insulin sensitivity in obese/ Type 2 Diabetic (T2D) individuals. However, some obese and T2D individuals do not respond well to regular exercise in their metabolic health. Purpose: The purpose of this study was to test the hypothesis that contractile activity in severely obese individuals (40>BMI) with T2D would be more blunted in insulin signaling and contraction-induced cellular activities in response to contractile activity compared to lean and severely obese individuals without T2D. Methods: Lean and healthy subjects (n=11) and severely obese individuals (BMI > 40) with T2D (n=8) and without T2D (n=8) were recruited. Skeletal muscle tissues were taken from each subject through muscle biopsy and differentiated in culture to myotubes to measure insulin sensitivity following contractile activity. The contractile activity was generated by electrical pulse stimulation (EPS) at 11.5 V, 2 ms, and 1Hz for 24 hours. Following EPS, myotubes were incubated with serum starvation media for 3 hours, then treated with insulin for 10 minutes, after which the cell lysate was harvested for western blot analysis to measure protein expression. Results: Phosphorylation of AMPK and ACC were significantly increased both in lean and severely obese group with EPS (P [less than] 0.05), but not in the T2D group. All participants from each group significantly increased (P [less than] 0.05) their insulin-mediated pAKT and pAS160 and the magnitude of insulin sensitivity was significantly higher (P [less than] 0.05) in the lean group compare to severely obese individuals with or without T2D. Interestingly, the insulin signaling was further increased (P [less than] 0.05) with insulin stimulation following EPS in only the lean group, but this effect was blunted in both severely obese with or without T2D. Conclusion: Our data show that EPS increases insulin signal transduction in myotubes from lean individuals, but this response is absent in myotubes from individuals with severe obesity with or without T2D. The T2D subjects show not only blunted insulin sensitivity but also impaired cellular energy pathways in response to contractile activity, indicating that there is an inherent defect in their cellular response to electrical/contractile activity in severely obese individuals with T2D

ENHANCED INSULIN SIGNALING FOLLOWING CONTRACTILE ACTIVITY IS BLUNTED IN MYOTUBES FROM SEVERELY OBESE INDIVIDUALS WITH OR WITHOUT TYPE 2 DIABETES

Introduction: Regular exercise has been known to improve insulin sensitivity in obese/ Type 2 Diabetic (T2D) individuals. However , some obese and T2D individuals do not respond well to regular exercise in their metabolic health. Purpose: The purpose of this study was to test the hypothesis that contractile activity in severely obese individuals (40>BMI) with T2D would be more blunted in insulin signaling and contraction-induced cellular activities in response to contractile activity compared to lean and severely obese individuals without T2D. Methods: Lean and healthy subjects (n=11) and severely obese individuals (BMI > 40) with T2D (n=8) and without T2D (n=8) were recruited. Skeletal muscle tissues were taken from each subject through muscle biopsy and differentiated in culture to myotubes to measure insulin sensitivity following contractile activity. The contractile activity was generated by electrical pulse stimulation (EPS) at 11.5 V , 2 ms , and 1Hz for 24 hours. Following EPS , myotubes were incubated with serum starvation media for 3 hours , then treated with insulin for 10 minutes , after which the cell lysate was harvested for western blot analysis to measure protein expression. Results: Phosphorylation of AMPK and ACC were significantly increased both in lean and severely obese group with EPS (P [less than] 0.05) , but not in the T2D group. All participants from each group significantly increased (P [less than] 0.05) their insulin-mediated pAKT and pAS160 and the magnitude of insulin sensitivity was significantly higher (P [less than] 0.05) in the lean group compare to severely obese individuals with or without T2D. Interestingly , the insulin signaling was further increased (P [less than] 0.05) with insulin stimulation following EPS in only the lean group , but this effect was blunted in both severely obese with or without T2D. Conclusion: Our data show that EPS increases insulin signal transduction in myotubes from lean individuals , but this response is absent in myotubes from individuals with severe obesity with or without T2D. The T2D subjects show not only blunted insulin sensitivity but also impaired cellular energy pathways in response to contractile activity , indicating that there is an inherent defect in their cellular response to electrical/contractile activity in severely obese individuals with T2D

The time-course of cancer cachexia onset reveals biphasic transcriptional disruptions in female skeletal muscle distinct from males

Abstract Background Cancer-cachexia (CC) is a debilitating condition affecting up to 80% of cancer patients and contributing to 40% of cancer-related deaths. While evidence suggests biological sex differences in the development of CC, assessments of the female transcriptome in CC are lacking, and direct comparisons between sexes are scarce. This study aimed to define the time course of Lewis lung carcinoma (LLC)-induced CC in females using transcriptomics, while directly comparing biological sex differences. Results We found the global gene expression of the gastrocnemius muscle of female mice revealed biphasic transcriptomic alterations, with one at 1 week following tumor allograft and another during the later stages of cachexia development. The early phase was associated with the upregulation of extracellular-matrix pathways, while the later phase was characterized by the downregulation of oxidative phosphorylation, electron transport chain, and TCA cycle. When DEGs were compared to a known list of mitochondrial genes (MitoCarta), ~ 47% of these genes were differently expressed in females exhibiting global cachexia, suggesting transcriptional changes to mitochondrial gene expression happens concomitantly to functional impairments previously published. In contrast, the JAK-STAT pathway was upregulated in both the early and late stages of CC. Additionally, we observed a consistent downregulation of Type-II Interferon signaling genes in females, which was associated with protection in skeletal muscle atrophy despite systemic cachexia. Upregulation of Interferon signaling was noted in the gastrocnemius muscle of cachectic and atrophic male mice. Comparison of female tumor-bearing mice with males revealed ~ 70% of DEGs were distinct between sexes in cachectic animals, demonstrating dimorphic mechanisms of CC. Conclusion Our findings suggest biphasic disruptions in the transcriptome of female LLC tumor-bearing mice: an early phase associated with ECM remodeling and a late phase, accompanied by the onset of systemic cachexia, affecting overall muscle energy metabolism. Notably, ~ 2/3 of DEGs in CC are biologically sex-specific, providing evidence of dimorphic mechanisms of cachexia between sexes. Downregulation of Type-II Interferon signaling genes appears specific to CC development in females, suggesting a new biological sex-specific marker of CC not reliant on the loss of muscle mass, that might represent a protective mechanism against muscle loss in CC in female mice

25th Annual Computational Neuroscience Meeting: CNS-2016

Table of contents A1 Functional advantages of cell-type heterogeneity in neural circuits Tatyana O. Sharpee A2 Mesoscopic modeling of propagating waves in visual cortex Alain Destexhe A3 Dynamics and biomarkers of mental disorders Mitsuo Kawato F1 Precise recruitment of spiking output at theta frequencies requires dendritic h-channels in multi-compartment models of oriens-lacunosum/moleculare hippocampal interneurons Vladislav Sekulić, Frances K. Skinner F2 Kernel methods in reconstruction of current sources from extracellular potentials for single cells and the whole brains Daniel K. Wójcik, Chaitanya Chintaluri, Dorottya Cserpán, Zoltán Somogyvári F3 The synchronized periods depend on intracellular transcriptional repression mechanisms in circadian clocks. Jae Kyoung Kim, Zachary P. Kilpatrick, Matthew R. Bennett, Kresimir Josić O1 Assessing irregularity and coordination of spiking-bursting rhythms in central pattern generators Irene Elices, David Arroyo, Rafael Levi, Francisco B. Rodriguez, Pablo Varona O2 Regulation of top-down processing by cortically-projecting parvalbumin positive neurons in basal forebrain Eunjin Hwang, Bowon Kim, Hio-Been Han, Tae Kim, James T. McKenna, Ritchie E. Brown, Robert W. McCarley, Jee Hyun Choi O3 Modeling auditory stream segregation, build-up and bistability James Rankin, Pamela Osborn Popp, John Rinzel O4 Strong competition between tonotopic neural ensembles explains pitch-related dynamics of auditory cortex evoked fields Alejandro Tabas, André Rupp, Emili Balaguer-Ballester O5 A simple model of retinal response to multi-electrode stimulation Matias I. Maturana, David B. Grayden, Shaun L. Cloherty, Tatiana Kameneva, Michael R. Ibbotson, Hamish Meffin O6 Noise correlations in V4 area correlate with behavioral performance in visual discrimination task Veronika Koren, Timm Lochmann, Valentin Dragoi, Klaus Obermayer O7 Input-location dependent gain modulation in cerebellar nucleus neurons Maria Psarrou, Maria Schilstra, Neil Davey, Benjamin Torben-Nielsen, Volker Steuber O8 Analytic solution of cable energy function for cortical axons and dendrites Huiwen Ju, Jiao Yu, Michael L. Hines, Liang Chen, Yuguo Yu O9 C. elegans interactome: interactive visualization of Caenorhabditis elegans worm neuronal network Jimin Kim, Will Leahy, Eli Shlizerman O10 Is the model any good? Objective criteria for computational neuroscience model selection Justas Birgiolas, Richard C. Gerkin, Sharon M. Crook O11 Cooperation and competition of gamma oscillation mechanisms Atthaphon Viriyopase, Raoul-Martin Memmesheimer, Stan Gielen O12 A discrete structure of the brain waves Yuri Dabaghian, Justin DeVito, Luca Perotti O13 Direction-specific silencing of the Drosophila gaze stabilization system Anmo J. Kim, Lisa M. Fenk, Cheng Lyu, Gaby Maimon O14 What does the fruit fly think about values? A model of olfactory associative learning Chang Zhao, Yves Widmer, Simon Sprecher,Walter Senn O15 Effects of ionic diffusion on power spectra of local field potentials (LFP) Geir Halnes, Tuomo Mäki-Marttunen, Daniel Keller, Klas H. Pettersen,Ole A. Andreassen, Gaute T. Einevoll O16 Large-scale cortical models towards understanding relationship between brain structure abnormalities and cognitive deficits Yasunori Yamada O17 Spatial coarse-graining the brain: origin of minicolumns Moira L. Steyn-Ross, D. Alistair Steyn-Ross O18 Modeling large-scale cortical networks with laminar structure Jorge F. Mejias, John D. Murray, Henry Kennedy, Xiao-Jing Wang O19 Information filtering by partial synchronous spikes in a neural population Alexandra Kruscha, Jan Grewe, Jan Benda, Benjamin Lindner O20 Decoding context-dependent olfactory valence in Drosophila Laurent Badel, Kazumi Ohta, Yoshiko Tsuchimoto, Hokto Kazama P1 Neural network as a scale-free network: the role of a hub B. Kahng P2 Hemodynamic responses to emotions and decisions using near-infrared spectroscopy optical imaging Nicoladie D. Tam P3 Phase space analysis of hemodynamic responses to intentional movement directions using functional near-infrared spectroscopy (fNIRS) optical imaging technique Nicoladie D.Tam, Luca Pollonini, George Zouridakis P4 Modeling jamming avoidance of weakly electric fish Jaehyun Soh, DaeEun Kim P5 Synergy and redundancy of retinal ganglion cells in prediction Minsu Yoo, S. E. Palmer P6 A neural field model with a third dimension representing cortical depth Viviana Culmone, Ingo Bojak P7 Network analysis of a probabilistic connectivity model of the Xenopus tadpole spinal cord Andrea Ferrario, Robert Merrison-Hort, Roman Borisyuk P8 The recognition dynamics in the brain Chang Sub Kim P9 Multivariate spike train analysis using a positive definite kernel Taro Tezuka P10 Synchronization of burst periods may govern slow brain dynamics during general anesthesia Pangyu Joo P11 The ionic basis of heterogeneity affects stochastic synchrony Young-Ah Rho, Shawn D. Burton, G. Bard Ermentrout, Jaeseung Jeong, Nathaniel N. Urban P12 Circular statistics of noise in spike trains with a periodic component Petr Marsalek P14 Representations of directions in EEG-BCI using Gaussian readouts Hoon-Hee Kim, Seok-hyun Moon, Do-won Lee, Sung-beom Lee, Ji-yong Lee, Jaeseung Jeong P15 Action selection and reinforcement learning in basal ganglia during reaching movements Yaroslav I. Molkov, Khaldoun Hamade, Wondimu Teka, William H. Barnett, Taegyo Kim, Sergey Markin, Ilya A. Rybak P17 Axon guidance: modeling axonal growth in T-Junction assay Csaba Forro, Harald Dermutz, László Demkó, János Vörös P19 Transient cell assembly networks encode persistent spatial memories Yuri Dabaghian, Andrey Babichev P20 Theory of population coupling and applications to describe high order correlations in large populations of interacting neurons Haiping Huang P21 Design of biologically-realistic simulations for motor control Sergio Verduzco-Flores P22 Towards understanding the functional impact of the behavioural variability of neurons Filipa Dos Santos, Peter Andras P23 Different oscillatory dynamics underlying gamma entrainment deficits in schizophrenia Christoph Metzner, Achim Schweikard, Bartosz Zurowski P24 Memory recall and spike frequency adaptation James P. Roach, Leonard M. Sander, Michal R. Zochowski P25 Stability of neural networks and memory consolidation preferentially occur near criticality Quinton M. Skilling, Nicolette Ognjanovski, Sara J. Aton, Michal Zochowski P26 Stochastic Oscillation in Self-Organized Critical States of Small Systems: Sensitive Resting State in Neural Systems Sheng-Jun Wang, Guang Ouyang, Jing Guang, Mingsha Zhang, K. Y. Michael Wong, Changsong Zhou P27 Neurofield: a C++ library for fast simulation of 2D neural field models Peter A. Robinson, Paula Sanz-Leon, Peter M. Drysdale, Felix Fung, Romesh G. Abeysuriya, Chris J. Rennie, Xuelong Zhao P28 Action-based grounding: Beyond encoding/decoding in neural code Yoonsuck Choe, Huei-Fang Yang P29 Neural computation in a dynamical system with multiple time scales Yuanyuan Mi, Xiaohan Lin, Si Wu P30 Maximum entropy models for 3D layouts of orientation selectivity Joscha Liedtke, Manuel Schottdorf, Fred Wolf P31 A behavioral assay for probing computations underlying curiosity in rodents Yoriko Yamamura, Jeffery R. Wickens P32 Using statistical sampling to balance error function contributions to optimization of conductance-based models Timothy Rumbell, Julia Ramsey, Amy Reyes, Danel Draguljić, Patrick R. Hof, Jennifer Luebke, Christina M. Weaver P33 Exploration and implementation of a self-growing and self-organizing neuron network building algorithm Hu He, Xu Yang, Hailin Ma, Zhiheng Xu, Yuzhe Wang P34 Disrupted resting state brain network in obese subjects: a data-driven graph theory analysis Kwangyeol Baek, Laurel S. Morris, Prantik Kundu, Valerie Voon P35 Dynamics of cooperative excitatory and inhibitory plasticity Everton J. Agnes, Tim P. Vogels P36 Frequency-dependent oscillatory signal gating in feed-forward networks of integrate-and-fire neurons William F. Podlaski, Tim P. Vogels P37 Phenomenological neural model for adaptation of neurons in area IT Martin Giese, Pradeep Kuravi, Rufin Vogels P38 ICGenealogy: towards a common topology of neuronal ion channel function and genealogy in model and experiment Alexander Seeholzer, William Podlaski, Rajnish Ranjan, Tim Vogels P39 Temporal input discrimination from the interaction between dynamic synapses and neural subthreshold oscillations Joaquin J. Torres, Fabiano Baroni, Roberto Latorre, Pablo Varona P40 Different roles for transient and sustained activity during active visual processing Bart Gips, Eric Lowet, Mark J. Roberts, Peter de Weerd, Ole Jensen, Jan van der Eerden P41 Scale-free functional networks of 2D Ising model are highly robust against structural defects: neuroscience implications Abdorreza Goodarzinick, Mohammad D. Niry, Alireza Valizadeh P42 High frequency neuron can facilitate propagation of signal in neural networks Aref Pariz, Shervin S. Parsi, Alireza Valizadeh P43 Investigating the effect of Alzheimer’s disease related amyloidopathy on gamma oscillations in the CA1 region of the hippocampus Julia M. Warburton, Lucia Marucci, Francesco Tamagnini, Jon Brown, Krasimira Tsaneva-Atanasova P44 Long-tailed distributions of inhibitory and excitatory weights in a balanced network with eSTDP and iSTDP Florence I. Kleberg, Jochen Triesch P45 Simulation of EMG recording from hand muscle due to TMS of motor cortex Bahar Moezzi, Nicolangelo Iannella, Natalie Schaworonkow, Lukas Plogmacher, Mitchell R. Goldsworthy, Brenton Hordacre, Mark D. McDonnell, Michael C. Ridding, Jochen Triesch P46 Structure and dynamics of axon network formed in primary cell culture Martin Zapotocky, Daniel Smit, Coralie Fouquet, Alain Trembleau P47 Efficient signal processing and sampling in random networks that generate variability Sakyasingha Dasgupta, Isao Nishikawa, Kazuyuki Aihara, Taro Toyoizumi P48 Modeling the effect of riluzole on bursting in respiratory neural networks Daniel T. Robb, Nick Mellen, Natalia Toporikova P49 Mapping relaxation training using effective connectivity analysis Rongxiang Tang, Yi-Yuan Tang P50 Modeling neuron oscillation of implicit sequence learning Guangsheng Liang, Seth A. Kiser, James H. Howard, Jr., Yi-Yuan Tang P51 The role of cerebellar short-term synaptic plasticity in the pathology and medication of downbeat nystagmus Julia Goncharenko, Neil Davey, Maria Schilstra, Volker Steuber P52 Nonlinear response of noisy neurons Sergej O. Voronenko, Benjamin Lindner P53 Behavioral embedding suggests multiple chaotic dimensions underlie C. elegans locomotion Tosif Ahamed, Greg Stephens P54 Fast and scalable spike sorting for large and dense multi-electrodes recordings Pierre Yger, Baptiste Lefebvre, Giulia Lia Beatrice Spampinato, Elric Esposito, Marcel Stimberg et Olivier Marre P55 Sufficient sampling rates for fast hand motion tracking Hansol Choi, Min-Ho Song P56 Linear readout of object manifolds SueYeon Chung, Dan D. Lee, Haim Sompolinsky P57 Differentiating models of intrinsic bursting and rhythm generation of the respiratory pre-Bötzinger complex using phase response curves Ryan S. Phillips, Jeffrey Smith P58 The effect of inhibitory cell network interactions during theta rhythms on extracellular field potentials in CA1 hippocampus Alexandra Pierri Chatzikalymniou, Katie Ferguson, Frances K. Skinner P59 Expansion recoding through sparse sampling in the cerebellar input layer speeds learning N. Alex Cayco Gajic, Claudia Clopath, R. Angus Silver P60 A set of curated cortical models at multiple scales on Open Source Brain Padraig Gleeson, Boris Marin, Sadra Sadeh, Adrian Quintana, Matteo Cantarelli, Salvador Dura-Bernal, William W. Lytton, Andrew Davison, R. Angus Silver P61 A synaptic story of dynamical information encoding in neural adaptation Luozheng Li, Wenhao Zhang, Yuanyuan Mi, Dahui Wang, Si Wu P62 Physical modeling of rule-observant rodent behavior Youngjo Song, Sol Park, Ilhwan Choi, Jaeseung Jeong, Hee-sup Shin P64 Predictive coding in area V4 and prefrontal cortex explains dynamic discrimination of partially occluded shapes Hannah Choi, Anitha Pasupathy, Eric Shea-Brown P65 Stability of FORCE learning on spiking and rate-based networks Dongsung Huh, Terrence J. Sejnowski P66 Stabilising STDP in striatal neurons for reliable fast state recognition in noisy environments Simon M. Vogt, Arvind Kumar, Robert Schmidt P67 Electrodiffusion in one- and two-compartment neuron models for characterizing cellular effects of electrical stimulation Stephen Van Wert, Steven J. Schiff P68 STDP improves speech recognition capabilities in spiking recurrent circuits parameterized via differential evolution Markov Chain Monte Carlo Richard Veale, Matthias Scheutz P69 Bidirectional transformation between dominant cortical neural activities and phase difference distributions Sang Wan Lee P70 Maturation of sensory networks through homeostatic structural plasticity Júlia Gallinaro, Stefan Rotter P71 Corticothalamic dynamics: structure, number of solutions and stability of steady-state solutions in the space of synaptic couplings Paula Sanz-Leon, Peter A. Robinson P72 Optogenetic versus electrical stimulation of the parkinsonian basal ganglia. Computational study Leonid L. Rubchinsky, Chung Ching Cheung, Shivakeshavan Ratnadurai-Giridharan P73 Exact spike-timing distribution reveals higher-order interactions of neurons Safura Rashid Shomali, Majid Nili Ahmadabadi, Hideaki Shimazaki, S. Nader Rasuli P74 Neural mechanism of visual perceptual learning using a multi-layered neural network Xiaochen Zhao, Malte J. Rasch P75 Inferring collective spiking dynamics from mostly unobserved systems Jens Wilting, Viola Priesemann P76 How to infer distributions in the brain from subsampled observations Anna Levina, Viola Priesemann P77 Influences of embedding and estimation strategies on the inferred memory of single spiking neurons Lucas Rudelt, Joseph T. Lizier, Viola Priesemann P78 A nearest-neighbours based estimator for transfer entropy between spike trains Joseph T. Lizier, Richard E. Spinney, Mikail Rubinov, Michael Wibral, Viola Priesemann P79 Active learning of psychometric functions with multinomial logistic models Ji Hyun Bak, Jonathan Pillow P81 Inferring low-dimensional network dynamics with variational latent Gaussian process Yuan Zaho, Il Memming Park P82 Computational investigation of energy landscapes in the resting state subcortical brain network Jiyoung Kang, Hae-Jeong Park P83 Local repulsive interaction between retinal ganglion cells can generate a consistent spatial periodicity of orientation map Jaeson Jang, Se-Bum Paik P84 Phase duration of bistable perception reveals intrinsic time scale of perceptual decision under noisy condition Woochul Choi, Se-Bum Paik P85 Feedforward convergence between retina and primary visual cortex can determine the structure of orientation map Changju Lee, Jaeson Jang, Se-Bum Paik P86 Computational method classifying neural network activity patterns for imaging data Min Song, Hyeonsu Lee, Se-Bum Paik P87 Symmetry of spike-timing-dependent-plasticity kernels regulates volatility of memory Youngjin Park, Woochul Choi, Se-Bum Paik P88 Effects of time-periodic coupling strength on the first-spike latency dynamics of a scale-free network of stochastic Hodgkin-Huxley neurons Ergin Yilmaz, Veli Baysal, Mahmut Ozer P89 Spectral properties of spiking responses in V1 and V4 change within the trial and are highly relevant for behavioral performance Veronika Koren, Klaus Obermayer P90 Methods for building accurate models of individual neurons Daniel Saska, Thomas Nowotny P91 A full size mathematical model of the early olfactory system of honeybees Ho Ka Chan, Alan Diamond, Thomas Nowotny P92 Stimulation-induced tuning of ongoing oscillations in spiking neural networks Christoph S. Herrmann, Micah M. Murray, Silvio Ionta, Axel Hutt, Jérémie Lefebvre P93 Decision-specific sequences of neural activity in balanced random networks driven by structured sensory input Philipp Weidel, Renato Duarte, Abigail Morrison P94 Modulation of tuning induced by abrupt reduction of SST cell activity Jung H. Lee, Ramakrishnan Iyer, Stefan Mihalas P95 The functional role of VIP cell activation during locomotion Jung H. Lee, Ramakrishnan Iyer, Christof Koch, Stefan Mihalas P96 Stochastic inference with spiking neural networks Mihai A. Petrovici, Luziwei Leng, Oliver Breitwieser, David Stöckel, Ilja Bytschok, Roman Martel, Johannes Bill, Johannes Schemmel, Karlheinz Meier P97 Modeling orientation-selective electrical stimulation with retinal prostheses Timothy B. Esler, Anthony N. Burkitt, David B. Grayden, Robert R. Kerr, Bahman Tahayori, Hamish Meffin P98 Ion channel noise can explain firing correlation in auditory nerves Bahar Moezzi, Nicolangelo Iannella, Mark D. 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