A database of computational models of a half-center oscillator for analyzing how neuronal parameters influence network activity

A half-center oscillator (HCO) is a common circuit building block of central pattern generator networks that produce rhythmic motor patterns in animals. Here we constructed an efficient relational database table with the resulting characteristics of the Hill et al.’s (J Comput Neurosci 10:281–302, 2001) HCO simple conductance-based model. The model consists of two reciprocally inhibitory neurons and replicates the electrical activity of the oscillator interneurons of the leech heartbeat central pattern generator under a variety of experimental conditions. Our long-range goal is to understand how this basic circuit building block produces functional activity under a variety of parameter regimes and how different parameter regimes influence stability and modulatability. By using the latest developments in computer technology, we simulated and stored large amounts of data (on the order of terabytes). We systematically explored the parameter space of the HCO and corresponding isolated neuron models using a brute-force approach. We varied a set of selected parameters (maximal conductance of intrinsic and synaptic currents) in all combinations, resulting in about 10 million simulations. We classified these HCO and isolated neuron model simulations by their activity characteristics into identifiable groups and quantified their prevalence. By querying the database, we compared the activity characteristics of the identified groups of our simulated HCO models with those of our simulated isolated neuron models and found that regularly bursting neurons compose only a small minority of functional HCO models; the vast majority was composed of spiking neurons.

[1]  A. Hodgkin,et al.  A quantitative description of membrane current and its application to conduction and excitation in nerve , 1990 .

[2]  Anders Lansner,et al.  Biophysically detailed modelling of microcircuits and beyond , 2005, Trends in Neurosciences.

[3]  Ronald L Calabrese,et al.  Heartbeat control in leeches. I. Constriction pattern and neural modulation of blood pressure in intact animals. , 2004, Journal of neurophysiology.

[4]  R. Calabrese,et al.  Using constraints on neuronal activity to reveal compensatory changes in neuronal parameters. , 2007, Journal of neurophysiology.

[5]  Astrid A Prinz,et al.  Insights from models of rhythmic motor systems , 2006, Current Opinion in Neurobiology.

[6]  Cengiz Günay,et al.  Channel Density Distributions Explain Spiking Variability in the Globus Pallidus: A Combined Physiology and Computer Simulation Database Approach , 2008, The Journal of Neuroscience.

[7]  E. F. CODD,et al.  A relational model of data for large shared data banks , 1970, CACM.

[8]  Ronald L. Calabrese,et al.  Oscillatory behaviors in pharmacologically isolated heart interneurons from the medicinal leech , 2000, Neurocomputing.

[9]  Ramez Elmasri,et al.  Fundamentals of database systems (2nd ed.) , 1994 .

[10]  Ronald L. Calabrese,et al.  A model of slow plateau-like oscillations based upon the fast Na+ current in a window mode , 2001, Neurocomputing.

[11]  Robert J Calin-Jageman,et al.  Parameter space analysis suggests multi-site plasticity contributes to motor pattern initiation in Tritonia. , 2007, Journal of neurophysiology.

[12]  E. Marder,et al.  Principles of rhythmic motor pattern generation. , 1996, Physiological reviews.

[13]  J. Bower,et al.  Exploring parameter space in detailed single neuron models: simulations of the mitral and granule cells of the olfactory bulb. , 1993, Journal of neurophysiology.

[14]  Paolo Dario,et al.  Modeling a vertebrate motor system: pattern generation, steering and control of body orientation. , 2007, Progress in brain research.

[15]  Cengiz Günay,et al.  Database Analysis of Simulated and Recorded Electrophysiological Datasets with PANDORA’s Toolbox , 2009, Neuroinformatics.

[16]  Holk Cruse,et al.  Motor pattern generation , 1998 .

[17]  E. Marder,et al.  Similar network activity from disparate circuit parameters , 2004, Nature Neuroscience.

[18]  M. A. Masino,et al.  Bursting in Leech Heart Interneurons: Cell-Autonomous and Network-Based Mechanisms , 2002, The Journal of Neuroscience.

[19]  Ramez Elmasri,et al.  Fundamentals of Database Systems , 1989 .

[20]  Eve Marder,et al.  Alternative to hand-tuning conductance-based models: construction and analysis of databases of model neurons. , 2003, Journal of neurophysiology.

[21]  Ronald L. Calabrese,et al.  How Does Maintenance of Network Activity Depend on Endogenous Dynamics of Isolated Neurons? , 2009, Neural Computation.

[22]  J. Bower,et al.  The Book of GENESIS , 1998, Springer New York.

[23]  Michael A. Arbib,et al.  The handbook of brain theory and neural networks , 1995, A Bradford book.

[24]  E. Marder,et al.  Invertebrate Central Pattern Generation Moves along , 2005, Current Biology.

[25]  Ronald L. Calabrese,et al.  The neural control of alternate heartbeat coordination states in the leech,Hirudo medicinalis , 2004, Journal of comparative physiology.

[26]  J. Lu,et al.  A Model of a Segmental Oscillator in the Leech Heartbeat Neuronal Network , 2001, Journal of Computational Neuroscience.

[27]  E. Marder,et al.  Variability, compensation and homeostasis in neuron and network function , 2006, Nature Reviews Neuroscience.

[28]  W. O. Friesen,et al.  Neuronal control of leech behavior , 2005, Progress in Neurobiology.