Optogenetics and Deep Brain Stimulation Neurotechnologies

  • Krishnakanth Kondabolu
  • Marek Mateusz Kowalski
  • Erik Andrew Roberts
  • Xue HanEmail author
Part of the Handbook of Experimental Pharmacology book series (HEP, volume 228)


Brain neural network is composed of densely packed, intricately wired neurons whose activity patterns ultimately give rise to every behavior, thought, or emotion that we experience. Over the past decade, a novel neurotechnique, optogenetics that combines light and genetic methods to control or monitor neural activity patterns, has proven to be revolutionary in understanding the functional role of specific neural circuits. We here briefly describe recent advance in optogenetics and compare optogenetics with deep brain stimulation technology that holds the promise for treating many neurological and psychiatric disorders.


Optogenetics Rhodopsin Channelrhodopsin Archaerhodopsin Deep brain stimulation 


  1. Anderson VC, Burchiel KJ et al (2005) Pallidal vs subthalamic nucleus deep brain stimulation in Parkinson disease. Arch Neurol 62(4):554–560CrossRefPubMedGoogle Scholar
  2. Bamann C, Gueta R et al (2010) Structural guidance of the photocycle of channelrhodopsin-2 by an interhelical hydrogen bond. Biochemistry 49(2):267–278CrossRefPubMedGoogle Scholar
  3. Bekar L, Libionka W et al (2008) Adenosine is crucial for deep brain stimulation-mediated attenuation of tremor. Nat Med 14(1):75–80CrossRefPubMedGoogle Scholar
  4. Berndt A, Schoenenberger P et al (2011) High-efficiency channelrhodopsins for fast neuronal stimulation at low light levels. Proc Natl Acad Sci U S A 108(18):7595–7600CrossRefPubMedCentralPubMedGoogle Scholar
  5. Berndt A, Lee SY et al (2014) Structure-guided transformation of channelrhodopsin into a light-activated chloride channel. Science 344(6182):420–424CrossRefPubMedCentralPubMedGoogle Scholar
  6. Bernstein JG, Boyden ES (2011) Optogenetic tools for analyzing the neural circuits of behavior. Trends Cogn Sci 15(12):592–600CrossRefPubMedCentralPubMedGoogle Scholar
  7. Bernstein JG, Han X et al (2008) Prosthetic systems for therapeutic optical activation and silencing of genetically-targeted neurons. Proc Soc Photo Opt Instrum Eng 6854:68540HGoogle Scholar
  8. Bernstein JG, Garrity PA et al (2012) Optogenetics and thermogenetics: technologies for controlling the activity of targeted cells within intact neural circuits. Curr Opin Neurobiol 22(1):61–71CrossRefPubMedCentralPubMedGoogle Scholar
  9. Boraud T, Brown P et al (2005) Oscillations in the basal ganglia: the good, the bad, and the unexpected. In: Bolam JP, Ingham CA, Magill PJ (eds) The basal ganglia VIII, Vol 56. Springer, New York, pp 1–24Google Scholar
  10. Boyden ES, Zhang F et al (2005) Millisecond-timescale, genetically targeted optical control of neural activity. Nat Neurosci 8(9):1263–1268CrossRefPubMedGoogle Scholar
  11. Brown P, Oliviero A et al (2001) Dopamine dependency of oscillations between subthalamic nucleus and pallidum in Parkinson’s disease. J Neurosci 21(3):1033–1038PubMedGoogle Scholar
  12. Cavanaugh J, Monosov IE et al (2012) Optogenetic inactivation modifies monkey visuomotor behavior. Neuron 76(5):901–907CrossRefPubMedCentralPubMedGoogle Scholar
  13. Chen TW, Wardill TJ et al (2013) Ultrasensitive fluorescent proteins for imaging neuronal activity. Nature 499(7458):295–300CrossRefPubMedCentralPubMedGoogle Scholar
  14. Chow BY, Han X et al (2010) High-performance genetically targetable optical neural silencing by light-driven proton pumps. Nature 463(7277):98–102CrossRefPubMedCentralPubMedGoogle Scholar
  15. Chow BY, Han X et al (2012) Genetically encoded molecular tools for light-driven silencing of targeted neurons. Prog Brain Res 196:49–61CrossRefPubMedCentralPubMedGoogle Scholar
  16. Chuong AS, Miri ML et al (2014) Noninvasive optical inhibition with a red-shifted microbial rhodopsin. Nat Neurosci 17(8):1123–1129CrossRefPubMedCentralPubMedGoogle Scholar
  17. Doroudchi MM, Greenberg KP et al (2011) Virally delivered channelrhodopsin-2 safely and effectively restores visual function in multiple mouse models of blindness. Mol Ther 19(7):1220–1229CrossRefPubMedCentralPubMedGoogle Scholar
  18. Dostrovsky JO, Levy R et al (2000) Microstimulation-induced inhibition of neuronal firing in human globus pallidus. J Neurophysiol 84(1):570–574PubMedGoogle Scholar
  19. Foffani G, Ardolino G et al (2006) Subthalamic oscillatory activities at beta or higher frequency do not change after high-frequency DBS in Parkinson’s disease. Brain Res Bull 69(2):123–130CrossRefPubMedGoogle Scholar
  20. Gunaydin LA, Yizhar O et al (2010) Ultrafast optogenetic control. Nat Neurosci 13(3):387–392CrossRefPubMedGoogle Scholar
  21. Han X (2012a) In vivo application of optogenetics for neural circuit analysis. ACS Chem Neurosci 3(8):577–584CrossRefPubMedCentralPubMedGoogle Scholar
  22. Han X (2012b) Optogenetics in the nonhuman primate. Prog Brain Res 196:215–233CrossRefPubMedCentralPubMedGoogle Scholar
  23. Han X, Boyden ES (2007) Multiple-color optical activation, silencing, and desynchronization of neural activity, with single-spike temporal resolution. PLoS One 2(3):e299CrossRefPubMedCentralPubMedGoogle Scholar
  24. Han X, Qian X et al (2009) Millisecond-timescale optical control of neural dynamics in the nonhuman primate brain. Neuron 62(2):191–198CrossRefPubMedCentralPubMedGoogle Scholar
  25. Han X, Chow BY et al (2011) A high-light sensitivity optical neural silencer: development and application to optogenetic control of non-human primate cortex. Front Syst Neurosci 5:18CrossRefPubMedCentralPubMedGoogle Scholar
  26. Knopfel T, Boyden ES (eds) (2012) Optogenetics: tools for controlling and monitoring neuronal activity, Progress in brain research. Elsevier, AmsterdamGoogle Scholar
  27. Kuhn AA, Kempf F et al (2008) High-frequency stimulation of the subthalamic nucleus suppresses oscillatory beta activity in patients with Parkinson’s disease in parallel with improvement in motor performance. J Neurosci 28(24):6165–6173CrossRefPubMedGoogle Scholar
  28. Kuhn AA, Tsui A et al (2009) Pathological synchronisation in the subthalamic nucleus of patients with Parkinson’s disease relates to both bradykinesia and rigidity. Exp Neurol 215(2):380–387CrossRefPubMedGoogle Scholar
  29. Lehmkuhle MJ, Bhangoo SS et al (2009) The electrocorticogram signal can be modulated with deep brain stimulation of the subthalamic nucleus in the hemiparkinsonian rat. J Neurophysiol 102(3):1811–1820CrossRefPubMedCentralPubMedGoogle Scholar
  30. Levy R, Hutchison WD et al (2000) High-frequency synchronization of neuronal activity in the subthalamic nucleus of parkinsonian patients with limb tremor. J Neurosci 20(20):7766–7775PubMedGoogle Scholar
  31. Levy R, Ashby P et al (2002a) Dependence of subthalamic nucleus oscillations on movement and dopamine in Parkinson’s disease. Brain 125(Pt 6):1196–1209CrossRefPubMedGoogle Scholar
  32. Levy R, Hutchison WD et al (2002b) Synchronized neuronal discharge in the basal ganglia of parkinsonian patients is limited to oscillatory activity. J Neurosci 22(7):2855–2861PubMedGoogle Scholar
  33. Liu X, Ramirez S et al (2012) Optogenetic stimulation of a hippocampal engram activates fear memory recall. Nature 484(7394):381–385CrossRefPubMedCentralPubMedGoogle Scholar
  34. Luo D, Saltzman WM (2000) Synthetic DNA delivery systems. Nat Biotechnol 18(1):33–37CrossRefPubMedGoogle Scholar
  35. Madisen L, Mao T et al (2012) A toolbox of Cre-dependent optogenetic transgenic mice for light-induced activation and silencing. Nat Neurosci 15(5):793–802CrossRefPubMedCentralPubMedGoogle Scholar
  36. Miesenbock G (2011) Optogenetic control of cells and circuits. Annu Rev Cell Dev Biol 27:731–758CrossRefPubMedCentralPubMedGoogle Scholar
  37. Mobley J, Vo-Dinh T (2003) Optical properties of tissue. In: Vo-Dinh T (ed) Biomedical photonics handbook. CRC, Boca Raton, FL, pp 1–72Google Scholar
  38. Nagel G, Szellas T et al (2003) Channelrhodopsin-2, a directly light-gated cation-selective membrane channel. Proc Natl Acad Sci USA 100(24):13940–13945CrossRefPubMedCentralPubMedGoogle Scholar
  39. Oesterhelt D, Stoeckenius W (1971) Rhodopsin-like protein from the purple membrane of Halobacterium halobium. Nat New Biol 233(39):149–152CrossRefPubMedGoogle Scholar
  40. Oesterhelt D, Stoeckenius W (1973) Functions of a new photoreceptor membrane. Proc Natl Acad Sci USA 70(10):2853–2857CrossRefPubMedCentralPubMedGoogle Scholar
  41. Priori A, Foffani G et al (2004) Rhythm-specific pharmacological modulation of subthalamic activity in Parkinson’s disease. Exp Neurol 189(2):369–379CrossRefPubMedGoogle Scholar
  42. Rodriguez-Oroz MC, Obeso JA et al (2005) Bilateral deep brain stimulation in Parkinson’s disease: a multicentre study with 4 years follow-up. Brain 128(Pt 10):2240–2249CrossRefPubMedGoogle Scholar
  43. Sauer B, Henderson N (1988) Site-specific DNA recombination in mammalian cells by the Cre recombinase of bacteriophage P1. Proc Natl Acad Sci USA 85(14):5166–5170CrossRefPubMedCentralPubMedGoogle Scholar
  44. Silberstein P, Pogosyan A et al (2005) Cortico-cortical coupling in Parkinson’s disease and its modulation by therapy. Brain 128(Pt 6):1277–1291CrossRefPubMedGoogle Scholar
  45. Spudich JL (2006) The multitalented microbial sensory rhodopsins. Trends Microbiol 14(11):480–487CrossRefPubMedGoogle Scholar
  46. Spudich JL, Yang CS et al (2000) Retinylidene proteins: structures and functions from archaea to humans. Annu Rev Cell Dev Biol 16:365–392CrossRefPubMedGoogle Scholar
  47. Tsien JZ, Chen DF et al (1996) Subregion- and cell type-restricted gene knockout in mouse brain. Cell 87(7):1317–1326CrossRefPubMedGoogle Scholar
  48. Uc EY, Follett KA (2007) Deep brain stimulation in movement disorders. Semin Neurol 27(2):170–182CrossRefPubMedGoogle Scholar
  49. Volkmann J, Moro E et al (2006) Basic algorithms for the programming of deep brain stimulation in Parkinson’s disease. Mov Disord 21(Suppl 14):S284–S289CrossRefPubMedGoogle Scholar
  50. Waehler R, Russell SJ et al (2007) Engineering targeted viral vectors for gene therapy. Nat Rev Genet 8(8):573–587CrossRefPubMedGoogle Scholar
  51. Weinberger M, Hutchison WD et al (2009a) Pathological subthalamic nucleus oscillations in PD: can they be the cause of bradykinesia and akinesia? Exp Neurol 219(1):58–61CrossRefPubMedGoogle Scholar
  52. Weinberger M, Hutchison WD et al (2009b) Increased gamma oscillatory activity in the subthalamic nucleus during tremor in Parkinson’s disease patients. J Neurophysiol 101(2):789–802CrossRefPubMedGoogle Scholar
  53. Wells J, Kao C et al (2005) Optical stimulation of neural tissue in vivo. Opt Lett 30(5):504–506CrossRefPubMedGoogle Scholar
  54. Welter ML, Houeto JL et al (2004) Effects of high-frequency stimulation on subthalamic neuronal activity in parkinsonian patients. Arch Neurol 61(1):89–96CrossRefPubMedGoogle Scholar
  55. Wietek J, Wiegert JS et al (2014) Conversion of channelrhodopsin into a light-gated chloride channel. Science 344(6182):409–412CrossRefPubMedGoogle Scholar
  56. Williams D, Tijssen M et al (2002) Dopamine-dependent changes in the functional connectivity between basal ganglia and cerebral cortex in humans. Brain 125(Pt 7):1558–1569CrossRefPubMedGoogle Scholar
  57. Wingeier B, Tcheng T et al (2006) Intra-operative STN DBS attenuates the prominent beta rhythm in the STN in Parkinson’s disease. Exp Neurol 197(1):244–251CrossRefPubMedGoogle Scholar
  58. Yizhar O, Fenno LE et al (2011) Optogenetics in neural systems. Neuron 71(1):9–34CrossRefPubMedGoogle Scholar
  59. Zhang F, Wang LP et al (2007) Multimodal fast optical interrogation of neural circuitry. Nature 446(7136):633–639CrossRefPubMedGoogle Scholar
  60. Zhang F, Vierock J et al (2011) The microbial opsin family of optogenetic tools. Cell 147(7):1446–1457CrossRefPubMedCentralPubMedGoogle Scholar
  61. Zhao S, Cunha C et al (2008) Improved expression of halorhodopsin for light-induced silencing of neuronal activity. Brain Cell Biol 36(1–4):141–154CrossRefPubMedCentralPubMedGoogle Scholar
  62. Zorzos AN, Dietrich A et al (2009) Light-proof neural recording electrodes. In: Poster presented at 39th society for neuroscience annual meeting, Chicago, 17–21 Oct 2009Google Scholar

Copyright information

© Springer International Publishing Switzerland 2015

Authors and Affiliations

  • Krishnakanth Kondabolu
    • 1
  • Marek Mateusz Kowalski
    • 1
  • Erik Andrew Roberts
    • 1
  • Xue Han
    • 1
    Email author
  1. 1.Biomedical Engineering DepartmentBoston UniversityBostonUSA

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