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POSTER PRESENTATION Open Access A novel model of an identified Drosophila crawl motoneuron for investigating functional effects of ion channel type across larval developmental stages Cengiz Günay 1* , Logesh Dharmar 1 , Fred Sieling 1,2 , Richard Baines 3 , Astrid A Prinz 1 From Twentieth Annual Computational Neuroscience Meeting: CNS*2011 Stockholm, Sweden. 23-28 July 2011 Drosophila is a powerful genetic model system for inves- tigating neuronal function. Most of the important mem- brane ion channel genes, such as voltage-gated sodium and potassium channels, were first identified and isolated in the fruit fly. Technical advances have now made possi- ble direct electrophysiological recording of channels in central neurons, allowing the genetic advantages of this system to be applied to analysis of cellular and circuit function and homeostasis. An important open question is the functional effect of channel splice variants that has recently been found in Drosophila neurons. Because of the experimental difficul- ties in the isolated expression of these splice variants, computational modeling becomes essential. In this work, we aim at assessing effects of Na channel splice variants [1] on neuronal activity by first building a full model neuron. For this full model neuron, parameters for individual ion channels are required. Previous literature on Drosophila ion channel parameters are highly variable. Taking an average of such disparate neuronal parameter values have been shown to be unideal [2]. Furthermore in our case, these data were collected from different neuronal types and preparations. We are thus focusing on identified larval aCC and RP2 abdominal dorsomedial motoneurons, which innervate the dorsal muscles [3], for building a novel full motoneuron model. We obtain their channel parameters by fitting models to experimental voltage- clamp data. We first present a minimal, isopotential spiking model neuron with transient and persistent sodium, delayed- rectifier, and A-type potassium channels. This model allows us to investigate the contributions of the two major types of A-type currents Shal and Shaker that are different in spatial expression over the neuron and in terms of electrophysiological and activity-related charac- teristics. We show how the Shal channel properties change between the larval stages of 1 st and 3 rd instar, and we show the effect of this change on neuronal activity characteristics. We then aim to add the calcium channel and potassium channels that are dependent on it. Overall, this neuron model will enable us to investigate the effect Na channel splice variants by varying half-activation and inactivation voltages and ratio of a persistent component. Acknowledgements Career Award at the Scientific Interface (CASI) from the Burroughs Wellcome Fund awarded to AAP. Experimental data was collected by Dr. Verena Wolfram and Dr. Richard Marley at University of Manchester, Manchester, U. K., and in Dr. Richard Levines lab at Arizona University, AZ, U.S.A. Dr. Robert Clewley and Dr. Marco Herrera-Valdez helped with modeling. Author details 1 Dept. Biology, Emory University, Atlanta, Georgia 30322, USA. 2 Biomedical Engineering Dept., Georgia Inst. Tech. And Emory Univ., Atlanta, Georgia, USA. 3 Life Sciences, University of Manchester, Manchester M13 9PT, UK. Published: 18 July 2011 References 1. Lin WH, Wright DE, Muraro NI, Baines RA: Alternative Splicing in the Voltage-Gated Sodium Channel DmNa(v) Regulates Activation, Inactivation, and Persistent Current. J. Neurophysiol 2009, 102(3):1994-2006. * Correspondence: [email protected] 1 Dept. Biology, Emory University, Atlanta, Georgia 30322, USA Full list of author information is available at the end of the article Günay et al. BMC Neuroscience 2011, 12(Suppl 1):P258 http://www.biomedcentral.com/1471-2202/12/S1/P258 © 2011 Günay 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 novel model of an identified Drosophila crawl motoneuron for investigating functional effects of ion channel type across larval developmental stages

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Page 1: A novel model of an identified Drosophila crawl motoneuron for investigating functional effects of ion channel type across larval developmental stages

POSTER PRESENTATION Open Access

A novel model of an identified Drosophila crawlmotoneuron for investigating functional effectsof ion channel type across larval developmentalstagesCengiz Günay1*, Logesh Dharmar1, Fred Sieling1,2, Richard Baines3, Astrid A Prinz1

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

Drosophila is a powerful genetic model system for inves-tigating neuronal function. Most of the important mem-brane ion channel genes, such as voltage-gated sodiumand potassium channels, were first identified and isolatedin the fruit fly. Technical advances have now made possi-ble direct electrophysiological recording of channels incentral neurons, allowing the genetic advantages of thissystem to be applied to analysis of cellular and circuitfunction and homeostasis.An important open question is the functional effect of

channel splice variants that has recently been found inDrosophila neurons. Because of the experimental difficul-ties in the isolated expression of these splice variants,computational modeling becomes essential. In this work,we aim at assessing effects of Na channel splice variants[1] on neuronal activity by first building a full modelneuron.For this full model neuron, parameters for individual ion

channels are required. Previous literature on Drosophilaion channel parameters are highly variable. Taking anaverage of such disparate neuronal parameter values havebeen shown to be unideal [2]. Furthermore in our case,these data were collected from different neuronal typesand preparations. We are thus focusing on identified larvalaCC and RP2 abdominal dorsomedial motoneurons,which innervate the dorsal muscles [3], for building anovel full motoneuron model. We obtain their channelparameters by fitting models to experimental voltage-clamp data.

We first present a minimal, isopotential spiking modelneuron with transient and persistent sodium, delayed-rectifier, and A-type potassium channels. This modelallows us to investigate the contributions of the twomajor types of A-type currents Shal and Shaker that aredifferent in spatial expression over the neuron and interms of electrophysiological and activity-related charac-teristics. We show how the Shal channel propertieschange between the larval stages of 1st and 3rd instar, andwe show the effect of this change on neuronal activitycharacteristics. We then aim to add the calcium channeland potassium channels that are dependent on it. Overall,this neuron model will enable us to investigate the effectNa channel splice variants by varying half-activation andinactivation voltages and ratio of a persistent component.

AcknowledgementsCareer Award at the Scientific Interface (CASI) from the Burroughs WellcomeFund awarded to AAP. Experimental data was collected by Dr. VerenaWolfram and Dr. Richard Marley at University of Manchester, Manchester, U.K., and in Dr. Richard Levine’s lab at Arizona University, AZ, U.S.A. Dr. RobertClewley and Dr. Marco Herrera-Valdez helped with modeling.

Author details1Dept. Biology, Emory University, Atlanta, Georgia 30322, USA. 2BiomedicalEngineering Dept., Georgia Inst. Tech. And Emory Univ., Atlanta, Georgia,USA. 3Life Sciences, University of Manchester, Manchester M13 9PT, UK.

Published: 18 July 2011

References1. Lin WH, Wright DE, Muraro NI, Baines RA: Alternative Splicing in the

Voltage-Gated Sodium Channel DmNa(v) Regulates Activation,Inactivation, and Persistent Current. J. Neurophysiol 2009,102(3):1994-2006.

* Correspondence: [email protected]. Biology, Emory University, Atlanta, Georgia 30322, USAFull list of author information is available at the end of the article

Günay et al. BMC Neuroscience 2011, 12(Suppl 1):P258http://www.biomedcentral.com/1471-2202/12/S1/P258

© 2011 Günay 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 novel model of an identified Drosophila crawl motoneuron for investigating functional effects of ion channel type across larval developmental stages

2. Golowasch J, Goldman M, Abbott L, Marder E: Failure of averaging in theconstruction of a conductance-based neuron model. J Neurophysiol 2002,87:1129-1131.

3. Landgraf M, Bossing T, Technau G, Bate M: The origin, location, andprojections of the embryonic abdominal motorneurons of Drosophila. J.Neurosci 1997, 17(24):9642-9655.

doi:10.1186/1471-2202-12-S1-P258Cite this article as: Günay et al.: A novel model of an identifiedDrosophila crawl motoneuron for investigating functional effects ofion channel type across larval developmental stages. BMC Neuroscience2011 12(Suppl 1):P258.

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