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POSTER PRESENTATION Open Access A generative model of the crab cardiac neuromuscular system with modulation Estee Stern 1* , Keyla García-Crescioni 2 , Mark W Miller 2 , Charles S Peskin 3 , Vladimir Brezina 1 From Twentieth Annual Computational Neuroscience Meeting: CNS*2011 Stockholm, Sweden. 23-28 July 2011 The neurogenic crab heart is driven by the cardiac gang- lion (CG), a central pattern generator that is embedded within the heart itself. The CG and the heart muscle form a complete closed-loop neuromuscular system. The bursting spike pattern generated by the CG drives the contractions of the muscle. These contractions, as well as previous spiking, then modify future spike gen- eration. The system is extensively regulated by numer- ous neuromodulators. Here, we present a model of the complete system, with and without modulation. We have modeled the system, at the level of spikes and contractions, as three processes: (1) the production of the contractions by the CG spikes, (2) the depen- dence of the CG spikes on the contractions, and (3) the dependence of the CG spikes on their own history. Using a system-identification method that we have developed [1], we first characterized each process sepa- rately from experimental data collected in the blue crab, Callinectes sapidus. Process (1) was characterized from spike-elicited contraction data in terms of three func- tions: K, the single-spike contraction kernel, H, a history kernel, and F, a static nonlinear function. These three functions successfully predict the contraction response to arbitrary spike trains. Using a modified version of the same method, we then characterized processes (2) and (3) together from data in which the CG spike pattern was recorded in response to stretches of the muscle. This gave three additional functions: K, a kernel describing the effect of muscle length change on the generation of CG spikes, H, a kernel describing the effect of a CG spike on the generation of future CG spikes, and F, another static nonlinear function. Finally, we repeated all of these steps using data collected in the presence of modulators to find, in each case, six modi- fied kernel functions. Combining the six unmodulated, or modulated, func- tions then gave a generative model of the complete car- diac system. This model exhibits a number of modes of spike generation, and resulting contraction, including multiple bursting modes, tonic firing, and no firing. It is likely that the modulators take the system from one mode to another. An example of a modeled shift induced by the addition of a modulator is shown in Fig. * Correspondence: [email protected] 1 Department of Neuroscience, Mount Sinai School of Medicine, New York, NY, USA Full list of author information is available at the end of the article Figure 1 An example of the activity of the generative model. The left column shows the activity when the six functions used in the model were obtained from unmodulated data. The voltageis the sum of the operations of the functions Kand Hthat can be roughly interpreted as reflecting the membrane voltage of the spiking neuron. The red dots indicate the spike times (grouped into bursts). The corresponding contraction amplitude is shown below. The right column shows the analogous results when the unmodulated functions K, H, and F were replaced with functions K, H, and F obtained from data with 10 -7 M CCAP. Stern et al. BMC Neuroscience 2011, 12(Suppl 1):P22 http://www.biomedcentral.com/1471-2202/12/S1/P22 © 2011 Stern et al; licensee BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

A generative model of the crab cardiac neuromuscular system with modulation

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POSTER PRESENTATION Open Access

A generative model of the crab cardiacneuromuscular system with modulationEstee Stern1*, Keyla García-Crescioni2, Mark W Miller2, Charles S Peskin3, Vladimir Brezina1

From Twentieth Annual Computational Neuroscience Meeting: CNS*2011Stockholm, Sweden. 23-28 July 2011

The neurogenic crab heart is driven by the cardiac gang-lion (CG), a central pattern generator that is embeddedwithin the heart itself. The CG and the heart muscleform a complete closed-loop neuromuscular system.The bursting spike pattern generated by the CG drivesthe contractions of the muscle. These contractions, aswell as previous spiking, then modify future spike gen-eration. The system is extensively regulated by numer-ous neuromodulators. Here, we present a model of thecomplete system, with and without modulation.We have modeled the system, at the level of spikes

and contractions, as three processes: (1) the productionof the contractions by the CG spikes, (2) the depen-dence of the CG spikes on the contractions, and (3) thedependence of the CG spikes on their own history.Using a system-identification method that we havedeveloped [1], we first characterized each process sepa-rately from experimental data collected in the blue crab,Callinectes sapidus. Process (1) was characterized fromspike-elicited contraction data in terms of three func-tions: K, the single-spike contraction kernel, H, a historykernel, and F, a static nonlinear function. These threefunctions successfully predict the contraction responseto arbitrary spike trains. Using a modified version of thesame method, we then characterized processes (2) and(3) together from data in which the CG spike patternwas recorded in response to stretches of the muscle.This gave three additional functions: K’, a kerneldescribing the effect of muscle length change on thegeneration of CG spikes, H’, a kernel describing theeffect of a CG spike on the generation of future CGspikes, and F’, another static nonlinear function. Finally,we repeated all of these steps using data collected in the

presence of modulators to find, in each case, six modi-fied kernel functions.Combining the six unmodulated, or modulated, func-

tions then gave a generative model of the complete car-diac system. This model exhibits a number of modes ofspike generation, and resulting contraction, includingmultiple bursting modes, tonic firing, and no firing. It islikely that the modulators take the system from onemode to another. An example of a modeled shiftinduced by the addition of a modulator is shown in Fig.

* Correspondence: [email protected] of Neuroscience, Mount Sinai School of Medicine, New York,NY, USAFull list of author information is available at the end of the article

Figure 1 An example of the activity of the generative model. Theleft column shows the activity when the six functions used in themodel were obtained from unmodulated data. The “voltage” is thesum of the operations of the functions K’ and H’ that can beroughly interpreted as reflecting the membrane voltage of thespiking neuron. The red dots indicate the spike times (grouped intobursts). The corresponding contraction amplitude is shown below.The right column shows the analogous results when theunmodulated functions K, H, and F were replaced with functions K,H, and F obtained from data with 10-7 M CCAP.

Stern et al. BMC Neuroscience 2011, 12(Suppl 1):P22http://www.biomedcentral.com/1471-2202/12/S1/P22

© 2011 Stern et al; licensee BioMed Central Ltd. This is an open access article distributed under the terms of the Creative CommonsAttribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction inany medium, provided the original work is properly cited.

Page 2: A generative model of the crab cardiac neuromuscular system with modulation

1, where the addition of crustacean cardioactive peptide(CCAP) shortens the cycle period by ~75%. The modelcan be used to better understand the global actions ofthe modulators and how their multiple actions allow thecardiac system to respond to physiological demands in arobust, yet flexible manner.

AcknowledgementsSupported by NS058017, NS41497, GM08224.

Author details1Department of Neuroscience, Mount Sinai School of Medicine, New York,NY, USA. 2Institute of Neurobiology, University of Puerto Rico MedicalSciences Campus, San Juan, PR, USA. 3Courant Institute of MathematicalSciences and Center for Neural Science, New York University, New York, NY,USA.

Published: 18 July 2011

Reference1. Stern E, Garcia-Crescioni K, Miller MW, Peskin CS, Brezina V: A Method for

decoding the neuromuscular spike-response transform. J NeurosciMethods 2009, 184:337-356.

doi:10.1186/1471-2202-12-S1-P22Cite this article as: Stern et al.: A generative model of the crab cardiacneuromuscular system with modulation. BMC Neuroscience 2011 12(Suppl1):P22.

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