Grossman, N

Jarvis, S

Nikolic, K

Schultz, S

BMC Neuroscience

English

PubMed

Spiral - Imperial College Digital Repository

POSTER PRESENTATION Open AccessControlling the neuronal balancing act:optical coactivation of excitation andinhibition in neuronal subdomainsSarah Jarvis1*, Konstantin Nikolic2, Nir Grossman2, Simon R Schultz1From Twenty Second Annual Computational Neuroscience Meeting: CNS*2013Paris, France. 13-18 July 2013Optogenetics provides a powerful tool with which to notonly observe but also manipulate neuronal activity, dueto the possibility to selectively activate spatially targetedsubpopulations of neurons. Much focus has been placedon excitatory opsins, such as channelrhodopsin-2(ChR2) [1], a light-gated cation channel which whenilluminated locally depolarizes the neuron membraneand can illicit an action potential (optimal activationwavelength l = 490nm). Previously, we investigated theeffect of illuminating targeting spatially distinct subdo-mains of the neuron for cortical layer V pyramidal neu-rons [2]. We demonstrated that whole cell, rather thanpartial, illumination had the highest efficiency for pro-ducing an action potential.More recently, the possibilities provided by ChR2 toprobe the kinetics of action potential generation werefurther complemented by the development of silencingopsins that hyperpolarize the membrane, includinghalorhodopsin (NpHR) [3] and Archaerhodopsin T(ArchT) [4]. Both HR and ArchT have been demon-strated in vivo to silence activity for populations, butthere has been little characterization of how they can beused to modulate action potential generation in indivi-dual neurons. As they can be illuminated independentlyof ChR2 (optimal activation wavelengths l = 585, 575for NpHR and ArchT respectively), together these twofamilies of opsins provide a potential window throughwhich to examine the interplay of competing excitatoryand inhibitory inputs for differing spatial and temporalpatterns of activation. Such characterization has implica-tions for advancing our understanding of the non-linearnature of inhibition, and is also vital for identifyingeffective protocols for silencing activity - especially whilethe spatial range and depth of illumination has experi-mental limitations that prevent deep or large areasbeing easily accessible. More importantly, it may allowmore subtle changes to be made to neuronal function,for instance by altering the transfer function of geneti-cally targeted classes of neurons.Here, we present the results of study in which we havemodeled neurons expressing NpHR and ArchT in NEU-RON. Using these models, we investigate common illu-mination strategies and examine the emergence of thesubthreshold dynamics by simultaneously illuminatingChR2 and silencing opsins, both for disjoint and identi-cal spatial locations. Finally, we activate silencing opsinswhile providing excitatory input via illumination ofChR2 in the proximal apical and basal dendrites,mimicking the location of excitatory presynapticsynapses in vivo. We demonstrate that it is possible to“reprogramme” the current-to-firing-rate transfer func-tion of a neuron [5], altering both gain and threshold ineither direction, by optical neuromodulation using acombination of ChR2 and ArchT or NpHR targeted toappropriate areas of the neuronal morphology. Usingthese results, we propose a more effective, targeted sti-mulation protocol for successfully inhibiting neuronalpopulations in cortical layers.AcknowledgementsThis work was supported by Wellcome Trust grant 097816/Z/11/A.Author details1Department of Bioengineering, Imperial College, London SW7 2AZ, UK.2Institute of Biomedical Engineering, Department of Electrical and ElectronicEngineering, Imperial College, London SW7 2AZ, UK.Published: 8 July 2013* Correspondence: s.jarvis@imperial.ac.uk1Department of Bioengineering, Imperial College, London SW7 2AZ, UKFull list of author information is available at the end of the articleJarvis et al. BMC Neuroscience 2013, 14(Suppl 1):P348http://www.biomedcentral.com/1471-2202/14/S1/P348© 2013 Jarvis 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.References1. Boyden ES, Zhang F, Bamberg E, Nagel G, Deisseroth K: Millisecond-timescale, genetically targeted optical control of neural activity. NatNeurosci 2005, 8(9):1263-1268.2. Grossman N, Simiaki V, Martinet C, Toumazou C, Schultz SR, Nikolic K:The spatial pattern of light determines the kinetics and modulatesbackpropagation of optogenetic action potentials. J Comp Neurosci 2012.3. Han X, Boyden ES: Multiple-color optical activation, silencing, anddesynchronization of neural activity, with single-spike temporalresolution. 2007, 2(3):e299, PLoS one.4. Han X, Chow BY, Zhou H, Klapoetke NC, Chuong A, Rajimehr R, Yang A,Baratta MV, Winkle J, Desimone R, Boyden ES: A high-light sensitivityoptical neural silencer: development and application to optogeneticcontrol of non-human primate cortex. Front Systems Neurosci 2011, 5:18.5. Chance FS, Abbott LF, Reyes AD: Gain modulation from backgroundsynaptic input. Neuron 2002, 35:773-782.doi:10.1186/1471-2202-14-S1-P348Cite this article as: Jarvis et al.: Controlling the neuronal balancing act:optical coactivation of excitation and inhibition in neuronalsubdomains. BMC Neuroscience 2013 14(Suppl 1):P348.Submit your next manuscript to BioMed Centraland take full advantage of: • Convenient online submission• Thorough peer review• No space constraints or color figure charges• Immediate publication on acceptance• Inclusion in PubMed, CAS, Scopus and Google Scholar• Research which is freely available for redistributionSubmit your manuscript at www.biomedcentral.com/submitJarvis et al. 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Controlling the neuronal balancing act: optical coactivation of excitation and inhibition in neuronal subdomains

http://dx.doi.org/10.1186/1471-2202-14-S1-P348

Controlling the neuronal balancing act: optical coactivation of excitation and inhibition in neuronal subdomains

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