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Issues in Clinical Epileptology: A View from the Bench pp 319–336Cite as

How Might Novel Technologies Such as Optogenetics Lead to Better Treatments in Epilepsy?

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Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 813))

Abstract

Recent technological advances open exciting avenues for improving the understanding of mechanisms in a broad range of epilepsies. This chapter focuses on the development of optogenetics and on-demand technologies for the study of epilepsy and the control of seizures. Optogenetics is a technique which, through cell-type selective expression of light-sensitive proteins called opsins, allows temporally precise control via light delivery of specific populations of neurons. Therefore, it is now possible not only to record interictal and ictal neuronal activity, but also to test causality and identify potential new therapeutic approaches. We first discuss the benefits and caveats to using optogenetic approaches and recent advances in optogenetics related tools. We then turn to the use of optogenetics, including on-demand optogenetics in the study of epilepsies, which highlights the powerful potential of optogenetics for epilepsy research.

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References

  1. Abaya TVF, Blair S, Tathireddy P, Rieth L, Solzbacher F (2012) A 3D glass optrode array for optical neural stimulation. Biomed Opt Express 3:3087–3104

    CAS  PubMed Central  PubMed  Google Scholar 

  2. Adesnik H, Bruns W, Taniguchi H, Huang ZJ, Scanziani M (2012) A neural circuit for spatial summation in visual cortex. Nature 490:226–231

    CAS  PubMed Central  PubMed  Google Scholar 

  3. Albus K, Wahab A, Heinemann U (2008) Standard antiepileptic drugs fail to block epileptiform activity in rat organotypic hippocampal slice cultures. Br J Pharmacol 154:709–724

    CAS  PubMed Central  PubMed  Google Scholar 

  4. Anikeeva P, Andalman AS, Witten I, Warden M, Goshen I, Grosenick L, Gunaydin LA, Frank LM, Deisseroth K (2012) Optetrode: a multichannel readout for optogenetic control in freely moving mice. Nat Neurosci 15:163–170

    CAS  Google Scholar 

  5. Arenkiel BR, Peca J, Davison IG, Feliciano C, Deisseroth K, Augustine GJ, Ehlers MD, Feng G (2007) In vivo light-induced activation of neural circuitry in transgenic mice expressing channelrhodopsin-2. Neuron 54:205–218

    CAS  PubMed Central  PubMed  Google Scholar 

  6. Armstrong C, Krook-Magnuson E, Oijala M, Soltesz I (2013) Closed-loop optogenetic intervention in mice. Nat Protoc 8:1475–1493

    CAS  PubMed Central  PubMed  Google Scholar 

  7. Armstrong C, Krook-Magnuson E, Soltesz I (2012) Neurogliaform and ivy cells: a major family of nNOS expressing GABAergic neurons. Front Neural Circuits 6:23

    CAS  PubMed Central  PubMed  Google Scholar 

  8. Armstrong C, Soltesz I (2012) Basket cell dichotomy in microcircuit function. J Physiol 590:683–694

    CAS  PubMed Central  PubMed  Google Scholar 

  9. Atasoy D, Aponte Y, Su HH, Sternson SM (2008) A FLEX switch targets channelrhodopsin-2 to multiple cell types for imaging and long-range circuit mapping. J Neurosci 28:7025–7030

    CAS  PubMed Central  PubMed  Google Scholar 

  10. Bartus RT, Baumann TL, Siffert J, Herzog CD, Alterman R, Boulis N, Turner DA, Stacy M, Lang AE, Lozano AM, Olanow CW (2013) Safety/feasibility of targeting the substantia nigra with AAV2-neurturin in Parkinson patients. Neurology 80:1698–1701

    CAS  PubMed Central  PubMed  Google Scholar 

  11. Bausch SB, McNamara JO (2000) Synaptic connections from multiple subfields contribute to granule cell hyperexcitability in hippocampal slice cultures. J Neurophysiol 84:2918–2932

    CAS  PubMed  Google Scholar 

  12. Bentley JN, Chestek C, Stacey WC, Patil PG (2013) Optogenetics in epilepsy. Neurosurg Focus 34:E4

    PubMed  Google Scholar 

  13. Berenyi A, Belluscio M, Mao D, Buzsaki G (2012) Closed-loop control of epilepsy by transcranial electrical stimulation. Science 337:735–737

    CAS  PubMed  Google Scholar 

  14. Berndt A, Schoenenberger P, Mattis J, Tye KM, Deisseroth K, Hegemann P, Oertner TG (2011) High-efficiency channelrhodopsins for fast neuronal stimulation at low light levels. Proc Natl Acad Sci U S A 108:7595–7600

    CAS  PubMed Central  PubMed  Google Scholar 

  15. Berndt A, Yizhar O, Gunaydin LA, Hegemann P, Deisseroth K (2009) Bi-stable neural state switches. Nat Neurosci 12:229–234

    CAS  PubMed  Google Scholar 

  16. Bezaire MJ, Soltesz I (2013) Quantitative assessment of CA1 local circuits: knowledge base for interneuron-pyramidal cell connectivity. Hippocampus 23:7595–7600

    Google Scholar 

  17. Bower MR, Buckmaster PS (2008) Changes in granule cell firing rates precede locally recorded spontaneous seizures by minutes in an animal model of temporal lobe epilepsy. J Neurophysiol 99:2431–2442

    PubMed  Google Scholar 

  18. Bower MR, Stead M, Meyer FB, Marsh WR, Worrell GA (2012) Spatiotemporal neuronal correlates of seizure generation in focal epilepsy. Epilepsia 53:807–816

    PubMed Central  PubMed  Google Scholar 

  19. Boyden ES, Zhang F, Bamberg E, Nagel G, Deisseroth K (2005) Millisecond-timescale, genetically targeted optical control of neural activity. Nat Neurosci 8:1263–1268

    CAS  PubMed  Google Scholar 

  20. Butt SJ, Fuccillo M, Nery S, Noctor S, Kriegstein A, Corbin JG, Fishell G (2005) The temporal and spatial origins of cortical interneurons predict their physiological subtype. Neuron 48:591–604

    CAS  PubMed  Google Scholar 

  21. Case MJ, Morgan RJ, Schneider CJ, Soltesz I (2012) Computer modeling of epilepsy. In: Jasper’s basic mechanisms of the epilepsies, 4th edn. Oxford, New York, pp 298–311

    Google Scholar 

  22. Chow BY, Han X, Dobry AS, Qian X, Chuong AS, Li M, Henninger MA, Belfort GM, Lin Y, Monahan PE, Boyden ES (2010) High-performance genetically targetable optical neural silencing by light-driven proton pumps. Nature 463:98–102

    CAS  PubMed Central  PubMed  Google Scholar 

  23. Chung K, Wallace J, Kim SY, Kalyanasundaram S, Andalman AS, Davidson TJ, Mirzabekov JJ, Zalocusky KA, Mattis J, Denisin AK, Pak S, Bernstein H, Ramakrishnan C, Grosenick L, Gradinaru V, Deisseroth K (2013) Structural and molecular interrogation of intact biological systems. Nature 497:332–337

    CAS  PubMed  Google Scholar 

  24. Cook MJ, O’Brien TJ, Berkovic SF, Murphy M, Morokoff A, Fabinyi G, D’Souza W, Yerra R, Archer J, Litewka L, Hosking S, Lightfoot P, Ruedebusch V, Sheffield WD, Snyder D, Leyde K, Himes D (2013) Prediction of seizure likelihood with a long-term, implanted seizure advisory system in patients with drug-resistant epilepsy: a first-in-man study. Lancet Neurol 12:563–571

    PubMed  Google Scholar 

  25. Corbin JG, Butt SJ (2011) Developmental mechanisms for the generation of telencephalic interneurons. Dev Neurobiol 71:710–732

    CAS  PubMed  Google Scholar 

  26. Drexel M, Kirchmair E, Wieselthaler-Holzl A, Preidt AP, Sperk G (2012) Somatostatin and neuropeptide Y neurons undergo different plasticity in parahippocampal regions in kainic acid-induced epilepsy. J Neuropathol Exp Neurol 71:312–329

    CAS  PubMed Central  PubMed  Google Scholar 

  27. Einevoll GT, Franke F, Hagen E, Pouzat C, Harris KD (2012) Towards reliable spike-train recordings from thousands of neurons with multielectrodes. Curr Opin Neurobiol 22:11–17

    CAS  PubMed Central  PubMed  Google Scholar 

  28. Engel J Jr, Thompson PM, Stern JM, Staba RJ, Bragin A, Mody I (2013) Connectomics and epilepsy. Curr Opin Neurol 26:186–194

    PubMed Central  PubMed  Google Scholar 

  29. Feldt Muldoon S, Soltesz I, Cossart R (2013) Spatially clustered neuronal assemblies comprise the microstructure of synchrony in chronically epileptic networks. Proc Natl Acad Sci U S A 110:3567–3572

    PubMed Central  PubMed  Google Scholar 

  30. Freund TF, Buzsaki G (1996) Interneurons of the hippocampus. Hippocampus 6:347–470

    CAS  PubMed  Google Scholar 

  31. Fuentealba P, Begum R, Capogna M, Jinno S, Marton LF, Csicsvari J, Thomson A, Somogyi P, Klausberger T (2008) Ivy cells: a population of nitric-oxide-producing, slow-spiking GABAergic neurons and their involvement in hippocampal network activity. Neuron 57:917–929

    CAS  PubMed  Google Scholar 

  32. Good LB, Sabesan S, Marsh ST, Tsakalis K, Treiman D, Iasemidis L (2009) Control of synchronization of brain dynamics leads to control of epileptic seizures in rodents. Int J Neural Syst 19:173–196

    PubMed Central  PubMed  Google Scholar 

  33. Gradinaru V, Thompson KR, Zhang F, Mogri M, Kay K, Schneider MB, Deisseroth K (2007) Targeting and readout strategies for fast optical neural control in vitro and in vivo. J Neurosci 27:14231–14238

    CAS  PubMed  Google Scholar 

  34. Gradinaru V, Zhang F, Ramakrishnan C, Mattis J, Prakash R, Diester I, Goshen I, Thompson KR, Deisseroth K (2010) Molecular and cellular approaches for diversifying and extending optogenetics. Cell 141:154–165

    CAS  PubMed  Google Scholar 

  35. Graves TD (2006) Ion channels and epilepsy. QJM 99:201–217

    CAS  PubMed  Google Scholar 

  36. Guenthner CJ, Miyamichi K, Yang HH, Heller HC, Luo L (2013) Permanent genetic access to transiently active neurons via TRAP: targeted recombination in active populations. Neuron 78:773–784

    CAS  PubMed Central  PubMed  Google Scholar 

  37. Gunaydin LA, Yizhar O, Berndt A, Sohal VS, Deisseroth K, Hegemann P (2010) Ultrafast optogenetic control. Nat Neurosci 13:387–392

    CAS  PubMed  Google Scholar 

  38. Han X, Chow BY, Zhou H, Klapoetke NC, Chuong A, Rajimehr R, Yang A, Baratta MV, Winkle J, Desimone R, Boyden ES (2011) A high-light sensitivity optical neural silencer: development and application to optogenetic control of non-human primate cortex. Front Syst Neurosci 5:18

    PubMed Central  PubMed  Google Scholar 

  39. Han X, Qian X, Bernstein JG, Zhou HH, Franzesi GT, Stern P, Bronson RT, Graybiel AM, Desimone R, Boyden ES (2009) Millisecond-timescale optical control of neural dynamics in the nonhuman primate brain. Neuron 62:191–198

    CAS  PubMed Central  PubMed  Google Scholar 

  40. Han X, Qian X, Stern P, Chuong AS, Boyden ES (2009) Informational lesions: optical perturbation of spike timing and neural synchrony via microbial opsin gene fusions. Front Mol Neurosci 2:12

    PubMed Central  PubMed  Google Scholar 

  41. Howard A, Tamas G, Soltesz I (2005) Lighting the chandelier: new vistas for axo-axonic cells. Trends Neurosci 28:310–316

    CAS  PubMed  Google Scholar 

  42. Hung C, Ling G, Mohanty SK, Chiao JJ (2013) An integrated μLED optrode for optogenetic stimulation and electrical recording. IEEE Trans Biomed Eng 60:225–229

    Google Scholar 

  43. Keller CJ, Truccolo W, Gale JT, Eskandar E, Thesen T, Carlson C, Devinsky O, Kuzniecky R, Doyle WK, Madsen JR, Schomer DL, Mehta AD, Brown EN, Hochberg LR, Ulbert I, Halgren E, Cash SS (2010) Heterogeneous neuronal firing patterns during interictal epileptiform discharges in the human cortex. Brain 133:1668–1681

    PubMed Central  PubMed  Google Scholar 

  44. Kim TI, McCall JG, Jung YH, Huang X, Siuda ER, Li Y, Song J, Song YM, Pao HA, Kim RH, Lu C, Lee SD, Song IS, Shin G, Al-Hasani R, Kim S, Tan MP, Huang Y, Omenetto FG, Rogers JA, Bruchas MR (2013) Injectable, cellular-scale optoelectronics with applications for wireless optogenetics. Science 340:211–216

    CAS  PubMed Central  PubMed  Google Scholar 

  45. Klausberger T, Somogyi P (2008) Neuronal diversity and temporal dynamics: the unity of hippocampal circuit operations. Science 321:53–57

    CAS  PubMed  Google Scholar 

  46. Kokaia M, Andersson M, Ledri M (2013) An optogenetic approach in epilepsy. Neuropharmacology 69:89–95

    CAS  PubMed  Google Scholar 

  47. Konermann S, Brigham MD, Trevino AE, Hsu PD, Heidenreich M, Cong L, Platt RJ, Scott DA, Church GM, Zhang F (2013) Optical control of mammalian endogenous transcription and epigenetic states. Nature 500:472–476

    CAS  PubMed  Google Scholar 

  48. Krook-Magnuson E, Armstrong C, Oijala M, Soltesz I (2013) On-demand optogenetic control of spontaneous seizures in temporal lobe epilepsy. Nat Commun 4:1376

    PubMed Central  PubMed  Google Scholar 

  49. Krook-Magnuson E, Varga C, Lee SH, Soltesz I (2012) New dimensions of interneuronal specialization unmasked by principal cell heterogeneity. Trends Neurosci 35:175–184

    CAS  PubMed Central  PubMed  Google Scholar 

  50. Ledri M, Nikitidou L, Erdelyi F, Szabo G, Kirik D, Deisseroth K, Kokaia M (2012) Altered profile of basket cell afferent synapses in hyper-excitable dentate gyrus revealed by optogenetic and two-pathway stimulations. Eur J Neurosci 36:1971–1983

    PubMed  Google Scholar 

  51. Lee G, Saito I (1998) Role of nucleotide sequences of loxP spacer region in Cre-mediated recombination. Gene 216:55–65

    CAS  PubMed  Google Scholar 

  52. Lee JH, Durand R, Gradinaru V, Zhang F, Goshen I, Kim DS, Fenno LE, Ramakrishnan C, Deisseroth K (2010) Global and local fMRI signals driven by neurons defined optogenetically by type and wiring. Nature 465:788–792

    CAS  PubMed Central  PubMed  Google Scholar 

  53. Lee SY, Soltesz I (2011) Cholecystokinin: a multi-functional molecular switch of neuronal circuits. Dev Neurobiol 71:83–91

    CAS  PubMed Central  PubMed  Google Scholar 

  54. Lin JY (2011) A user’s guide to channelrhodopsin variants: features, limitations and future developments. Exp Physiol 96:19–25

    PubMed Central  PubMed  Google Scholar 

  55. Lin JY, Lin MZ, Steinbach P, Tsien RY (2009) Characterization of engineered channelrhodopsin variants with improved properties and kinetics. Biophys J 96:1803–1814

    CAS  PubMed Central  PubMed  Google Scholar 

  56. Madisen L, Mao T, Koch H, Zhuo JM, Berenyi A, Fujisawa S, Hsu YW, Garcia AJ 3rd, Gu X, Zanella S, Kidney J, Gu H, Mao Y, Hooks BM, Boyden ES, Buzsaki G, Ramirez JM, Jones AR, Svoboda K, Han X, Turner EE, Zeng H (2012) A toolbox of Cre-dependent optogenetic transgenic mice for light-induced activation and silencing. Nat Neurosci 15:793–802

    CAS  PubMed Central  PubMed  Google Scholar 

  57. Maehara T (2007) Neuroimaging of epilepsy. Neuropathology 27:585–593

    PubMed  Google Scholar 

  58. Markert JM, Medlock MD, Rabkin SD, Gillespie GY, Todo T, Hunter WD, Palmer CA, Feigenbaum F, Tornatore C, Tufaro F, Martuza RL (2000) Conditionally replicating herpes simplex virus mutant, G207 for the treatment of malignant glioma: results of a phase I trial. Gene Ther 7:867–874

    CAS  PubMed  Google Scholar 

  59. Matta JA, Pelkey KA, Craig MT, Chittajallu R, Jeffries BW, McBain CJ (2013) Developmental origin dictates interneuron AMPA and NMDA receptor subunit composition and plasticity. Nat Neurosci 16:1032–1041

    CAS  PubMed  Google Scholar 

  60. Mattis J, Tye KM, Ferenczi EA, Ramakrishnan C, O’Shea DJ, Prakash R, Gunaydin LA, Hyun M, Fenno LE, Gradinaru V, Yizhar O, Deisseroth K (2012) Principles for applying optogenetic tools derived from direct comparative analysis of microbial opsins. Nat Methods 9:159–172

    CAS  Google Scholar 

  61. Merwick A, O’Brien M, Delanty N (2012) Complex single gene disorders and epilepsy. Epilepsia 53(Suppl 4):81–91

    CAS  PubMed  Google Scholar 

  62. Murphy AM, Rabkin SD (2013) Current status of gene therapy for brain tumors. Transl Res 161:339–354

    CAS  PubMed Central  PubMed  Google Scholar 

  63. Nagel G, Szellas T, Huhn W, Kateriya S, Adeishvili N, Berthold P, Ollig D, Hegemann P, Bamberg E (2003) Channelrhodopsin-2, a directly light-gated cation-selective membrane channel. Proc Natl Acad Sci U S A 100:13940–13945

    CAS  PubMed Central  PubMed  Google Scholar 

  64. Osawa S, Iwasaki M, Hosaka R, Matsuzaka Y, Tomita H, Ishizuka T, Sugano E, Okumura E, Yawo H, Nakasato N, Tominaga T, Mushiake H (2013) Optogenetically induced seizure and the longitudinal hippocampal network dynamics. PLoS One 8:e60928

    CAS  PubMed Central  PubMed  Google Scholar 

  65. Paz JT, Davidson TJ, Frechette ES, Delord B, Parada I, Peng K, Deisseroth K, Huguenard JR (2013) Closed-loop optogenetic control of thalamus as a tool for interrupting seizures after cortical injury. Nat Neurosci 16:64–70

    CAS  PubMed Central  PubMed  Google Scholar 

  66. Raimondo JV, Kay L, Ellender TJ, Akerman CJ (2012) Optogenetic silencing strategies differ in their effects on inhibitory synaptic transmission. Nat Neurosci 15:1102–1104

    CAS  PubMed Central  PubMed  Google Scholar 

  67. Richichi C, Lin EJ, Stefanin D, Colella D, Ravizza T, Grignaschi G, Veglianese P, Sperk G, During MJ, Vezzani A (2004) Anticonvulsant and antiepileptogenic effects mediated by adeno-associated virus vector neuropeptide Y expression in the rat hippocampus. J Neurosci 24:3051–3059

    CAS  PubMed  Google Scholar 

  68. Rothman SM (2009) The therapeutic potential of focal cooling for neocortical epilepsy. Neurotherapeutics 6:251–257

    PubMed  Google Scholar 

  69. Royer S, Zemelman BV, Barbic M, Losonczy A, Buzsaki G, Magee JC (2010) Multi-array silicon probes with integrated optical fibers: light-assisted perturbation and recording of local neural circuits in the behaving animal. Eur J Neurosci 31:2279–2291

    PubMed Central  PubMed  Google Scholar 

  70. Schneider CJ, Bezaire M, Soltesz I (2012) Toward a full-scale computational model of the rat dentate gyrus. Front Neural Circuits 6:83

    PubMed Central  PubMed  Google Scholar 

  71. Schnutgen F, Doerflinger N, Calleja C, Wendling O, Chambon P, Ghyselinck NB (2003) A directional strategy for monitoring Cre-mediated recombination at the cellular level in the mouse. Nat Biotechnol 21:562–565

    PubMed  Google Scholar 

  72. Smedemark-Margulies N, Trapani JG (2013) Tools, methods, and applications for optophysiology in neuroscience. Front Mol Neurosci 6:18

    PubMed Central  PubMed  Google Scholar 

  73. Soltesz I, Staley K (eds) (2008) Computational neuroscience in epilepsy. London/San Diego/Burlington

    Google Scholar 

  74. Sorensen AT, Nikitidou L, Ledri M, Lin EJ, During MJ, Kanter-Schlifke I, Kokaia M (2009) Hippocampal NPY gene transfer attenuates seizures without affecting epilepsy-induced impairment of LTP. Exp Neurol 215:328–333

    CAS  PubMed Central  PubMed  Google Scholar 

  75. Stark E, Koos T, Buzsaki G (2012) Diode probes for spatiotemporal optical control of multiple neurons in freely moving animals. J Neurophysiol 108:349–363

    PubMed Central  PubMed  Google Scholar 

  76. Sukhotinsky I, Chan AM, Ahmed OJ, Rao VR, Gradinaru V, Ramakrishnan C, Deisseroth K, Majewska AK, Cash SS (2013) Optogenetic delay of status epilepticus onset in an in vivo rodent epilepsy model. PLoS One 8:e62013

    CAS  PubMed Central  PubMed  Google Scholar 

  77. Takano H, Coulter DA (2012) Imaging of hippocampal circuits in epilepsy. In: Noebels JL, Avoli M, Rogawski MA et al (eds) Jasper’s basic mechanisms of the epilepsies, 4th edn. Oxford, New York, pp 190–201

    Google Scholar 

  78. Tamura K, Ohashi Y, Tsubota T, Takeuchi D, Hirabayashi T, Yaguchi M, Matsuyama M, Sekine T, Miyashita Y (2012) A glass-coated tungsten microelectrode enclosing optical fibers for optogenetic exploration in primate deep brain structures. J Neurosci Methods 211:49–57

    CAS  PubMed  Google Scholar 

  79. Tanaka KF, Matsui K, Sasaki T, Sano H, Sugio S, Fan K, Hen R, Nakai J, Yanagawa Y, Hasuwa H, Okabe M, Deisseroth K, Ikenaka K, Yamanaka A (2012) Expanding the repertoire of optogenetically targeted cells with an enhanced gene expression system. Cell Rep 2:397–406

    CAS  PubMed  Google Scholar 

  80. Taniguchi H, He M, Wu P, Kim S, Paik R, Sugino K, Kvitsiani D, Fu Y, Lu J, Lin Y, Miyoshi G, Shima Y, Fishell G, Nelson SB, Huang ZJ (2011) A resource of Cre driver lines for genetic targeting of GABAergic neurons in cerebral cortex. Neuron 71:995–1013

    CAS  PubMed Central  PubMed  Google Scholar 

  81. Taniguchi H, Lu J, Huang ZJ (2013) The spatial and temporal origin of chandelier cells in mouse neocortex. Science 339:70–74

    CAS  PubMed Central  PubMed  Google Scholar 

  82. Tomita H, Sugano E, Fukazawa Y, Isago H, Sugiyama Y, Hiroi T, Ishizuka T, Mushiake H, Kato M, Hirabayashi M, Shigemoto R, Yawo H, Tamai M (2009) Visual properties of transgenic rats harboring the channelrhodopsin-2 gene regulated by the thy-1.2 promoter. PLoS One 4:e7679

    PubMed Central  PubMed  Google Scholar 

  83. Toni N, Laplagne DA, Zhao C, Lombardi G, Ribak CE, Gage FH, Schinder AF (2008) Neurons born in the adult dentate gyrus form functional synapses with target cells. Nat Neurosci 11:901–907

    CAS  PubMed Central  PubMed  Google Scholar 

  84. Tonnesen J, Sorensen AT, Deisseroth K, Lundberg C, Kokaia M (2009) Optogenetic control of epileptiform activity. Proc Natl Acad Sci U S A 106:12162–12167

    CAS  PubMed Central  PubMed  Google Scholar 

  85. Truccolo W, Donoghue JA, Hochberg LR, Eskandar EN, Madsen JR, Anderson WS, Brown EN, Halgren E, Cash SS (2011) Single-neuron dynamics in human focal epilepsy. Nat Neurosci 14:635–641

    CAS  PubMed Central  PubMed  Google Scholar 

  86. Varga C, Lee SY, Soltesz I (2010) Target-selective GABAergic control of entorhinal cortex output. Nat Neurosci 13:822–824

    CAS  PubMed Central  PubMed  Google Scholar 

  87. Vezzani A (2007) The promise of gene therapy for the treatment of epilepsy. Expert Rev Neurother 7:1685–1692

    CAS  PubMed  Google Scholar 

  88. Visel A, Taher L, Girgis H, May D, Golonzhka O, Hoch RV, McKinsey GL, Pattabiraman K, Silberberg SN, Blow MJ, Hansen DV, Nord AS, Akiyama JA, Holt A, Hosseini R, Phouanenavong S, Plajzer-Frick I, Shoukry M, Afzal V, Kaplan T, Kriegstein AR, Rubin EM, Ovcharenko I, Pennacchio LA, Rubenstein JL (2013) A high-resolution enhancer atlas of the developing telencephalon. Cell 152:895–908

    CAS  PubMed Central  PubMed  Google Scholar 

  89. Wang J, Wagner F, Borton DA, Zhang J, Ozden I, Burwell RD, Nurmikko AV, Wagenen R, Diester I, Deisseroth K (2012) Integrated device for combined optical neuromodulation and electrical recording for chronic in vivo applications. J Neural Eng 9:016001

    PubMed  Google Scholar 

  90. Wentz CT, Bernstein JG, Monahan P, Guerra A, Rodriguez A, Boyden ES (2011) A wirelessly powered and controlled device for optical neural control of freely-behaving animals. J Neural Eng 8:046021

    PubMed Central  PubMed  Google Scholar 

  91. White AM, Williams PA, Ferraro DJ, Clark S, Kadam SD, Dudek FE, Staley KJ (2006) Efficient unsupervised algorithms for the detection of seizures in continuous EEG recordings from rats after brain injury. J Neurosci Methods 152:255–266

    PubMed  Google Scholar 

  92. Woodson W, Nitecka L, Ben-Ari Y (1989) Organization of the GABAergic system in the rat hippocampal formation: a quantitative immunocytochemical study. J Comp Neurol 280:254–271

    CAS  PubMed  Google Scholar 

  93. Wu C, Sharan AD (2013) Neurostimulation for the treatment of epilepsy: a review of current surgical interventions. Neuromodulation 16:10–24, discussion 24

    PubMed  Google Scholar 

  94. Wykes RC, Heeroma JH, Mantoan L, Zheng K, Macdonald DC, Deisseroth K, Hashemi KS, Walker MC, Schorge S, Kullmann DM (2012) Optogenetic and potassium channel gene therapy in a rodent model of focal neocortical epilepsy. Sci Transl Med 4:161ra152

    PubMed Central  PubMed  Google Scholar 

  95. Xu X, Olivas ND, Levi R, Ikrar T, Nenadic Z (2010) High precision and fast functional mapping of cortical circuitry through a novel combination of voltage sensitive dye imaging and laser scanning photostimulation. J Neurophysiol 103:2301–2312

    PubMed Central  PubMed  Google Scholar 

  96. Yang X, Rode DL, Peterka DS, Yuste R, Rothman SM (2012) Optical control of focal epilepsy in vivo with caged gamma-aminobutyric acid. Ann Neurol 71:68–75

    CAS  PubMed  Google Scholar 

  97. Yizhar O, Fenno LE, Prigge M, Schneider F, Davidson TJ, O’Shea DJ, Sohal VS, Goshen I, Finkelstein J, Paz JT, Stehfest K, Fudim R, Ramakrishnan C, Huguenard JR, Hegemann P, Deisseroth K (2011) Neocortical excitation/inhibition balance in information processing and social dysfunction. Nature 477:171–178

    CAS  PubMed  Google Scholar 

  98. Zhang F, Aravanis AM, Adamantidis A, de Lecea L, Deisseroth K (2007) Circuit-breakers: optical technologies for probing neural signals and systems. Nat Rev Neurosci 8:577–581

    CAS  PubMed  Google Scholar 

  99. Zhang F, Gradinaru V, Adamantidis AR, Durand R, Airan RD, de Lecea L, Deisseroth K (2010) Optogenetic interrogation of neural circuits: technology for probing mammalian brain structures. Nat Protoc 5:439–456

    CAS  PubMed  Google Scholar 

  100. Zhang F, Prigge M, Beyriere F, Tsunoda SP, Mattis J, Yizhar O, Hegemann P, Deisseroth K (2008) Red-shifted optogenetic excitation: a tool for fast neural control derived from Volvox carteri. Nat Neurosci 11:631–633

    PubMed Central  PubMed  Google Scholar 

  101. Zhang J, Laiwalla F, Kim JA, Urabe H, Wagenen RV, Song Y-K, Connors BW, Zhang F, Deisseroth K, Nurmikko AV (2009) Integrated device for optical stimulation and spatiotemporal electrical recording of neural activity in light-sensitized brain tissue. J Neural Eng 6:055007

    PubMed Central  PubMed  Google Scholar 

  102. Zhang YP, Oertner TG (2007) Optical induction of synaptic plasticity using a light-sensitive channel. Nat Methods 4:139–141

    CAS  PubMed  Google Scholar 

  103. Zhu P, Narita Y, Bundschuh ST, Fajardo O, Scharer YP, Chattopadhyaya B, Bouldoires EA, Stepien AE, Deisseroth K, Arber S, Sprengel R, Rijli FM, Friedrich RW (2009) Optogenetic dissection of neuronal circuits in zebrafish using viral gene transfer and the Tet system. Front Neural Circuits 3:21

    PubMed Central  PubMed  Google Scholar 

  104. Zorzos AN, Boyden ES, Fonstad CG (2010) Multiwaveguide implantable probe for light delivery to sets of distributed brain targets. Opt Lett 35:4133–4135

    PubMed Central  PubMed  Google Scholar 

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Acknowledgements

This chapter on optogenetic approaches to epilepsy highlights the fundamental veracity of Phil's overarching conceptual framework that placed a major emphasis on the critical importance of rigorous, quantitative mechanistic understanding of epileptic neuronal circuits in order to develop new generations of temporally and spatially selective, more effective seizure control strategies.

Other Acknowledgements

This work was supported by US National Institutes of Health grant NS74432 and the Swedish Brain Foundation.

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Authors and Affiliations

  1. Department of Anatomy and Neurobiology, University of California, 192 Irvine Hall, Irvine, CA, 92697, USA

    Esther Krook-Magnuson & Ivan Soltesz

  2. Experimental Epilepsy Group, Epilepsy Center, Department of Clinical Sciences, Lund University Hospital, Sölvegatan 17, BMC A11, 22184, Lund, Sweden

    Marco Ledri & Merab Kokaia

  3. Laboratory of Molecular Neurobiology, Department of Molecular and Developmental Neurobiology, Institute of Experimental Medicine, Hungarian Academy of Sciences, Szigony utca, 43, H-1083, Budapest, Hungary

    Marco Ledri

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  1. Esther Krook-Magnuson
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  2. Marco Ledri
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  3. Ivan Soltesz
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  4. Merab Kokaia
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Correspondence to Esther Krook-Magnuson .

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Editors and Affiliations

  1. Dept. of Child & Adoles. Psych., Phys. & Neurosc., and Psych., New York Univ. Langone Med. Ctr., Orangeburg, New York, USA

    Helen E. Scharfman

  2. Dept. of Comp. Med. and Neurol. & Neurol. Scs., Stanford University, Stanford, California, USA

    Paul S. Buckmaster

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Krook-Magnuson, E., Ledri, M., Soltesz, I., Kokaia, M. (2014). How Might Novel Technologies Such as Optogenetics Lead to Better Treatments in Epilepsy?. In: Scharfman, H., Buckmaster, P. (eds) Issues in Clinical Epileptology: A View from the Bench. Advances in Experimental Medicine and Biology, vol 813. Springer, Dordrecht. https://doi.org/10.1007/978-94-017-8914-1_26

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  • DOI: https://doi.org/10.1007/978-94-017-8914-1_26

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