Skip to main content

Controlling Behavior Using Light to Excite and Silence Neuronal Activity

  • Chapter
  • First Online:
  • 748 Accesses

Abstract

The number of reports involving the new tools of optogenetics is increasing exponentially to yield detailed insights into anatomical, physiological, and pathological issues. These tools help us to tackle major questions regarding the function of neural circuits in the mammalian brain, which possesses uncountable combinations of neurons. Moreover, rapid progress in diverse collaborations between optogenetics and optical imaging technologies will allow us to analyze, simultaneously, the activities of multiple neurons and glial cells. As well as activity analysis, optogenetics is developing rapidly to support the analysis of stimulation in neuronal function. We can now stimulate multiple cell types independently using selective molecular tools, such as promoters and gene delivery systems. In addition, optical properties also help us to discriminate among subpopulations of cells in neuronal networks. The use of light to study the brain has proved to be a remarkably fruitful strategy, and indeed optogenetics has given us a green light for the future.

This is a preview of subscription content, log in via an institution.

Buying options

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

References

  • Abbott SB, Stornetta RL, Fortuna MG et al (2009a) Photostimulation of retrotrapezoid nucleus phox2b-expressing neurons in vivo produces long-lasting activation of breathing in rats. J Neurosci 29:5806–5819

    Article  PubMed  CAS  Google Scholar 

  • Abbott SB, Stornetta RL, Socolovsky CS et al (2009b) Photostimulation of channelrhodopsin-2 expressing ventrolateral medullary neurons increases sympathetic nerve activity and blood pressure in rats. J Physiol 587:5613–5631

    Article  PubMed  CAS  Google Scholar 

  • Adamantidis AR, Zhang F, Aravanis AM et al (2007) Neural substrates of awakening probed with optogenetic control of hypocretin neurons. Nature 450:420–424

    Article  PubMed  CAS  Google Scholar 

  • Adesnik H, Scanziani M (2010) Lateral competition for cortical space by layer-specific horizontal circuits. Nature 464:1155–1160

    Article  PubMed  CAS  Google Scholar 

  • Airan RD, Thompson KR, Fenno LE et al (2009) Temporally precise in vivo control of intracellular signalling. Nature 458:1025–1029

    Article  PubMed  CAS  Google Scholar 

  • Alilain WJ, Li X, Horn KP et al (2008) Light-induced rescue of breathing after spinal cord injury. J Neurosci 28:11862–11870

    Article  PubMed  CAS  Google Scholar 

  • Aravanis AM, Wang LP, Zhang F et al (2007) An optical neural interface: in vivo control of rodent motor cortex with integrated fiberoptic and optogenetic technology. J Neural Eng 4:S143–56

    Article  PubMed  Google Scholar 

  • Bamann C, Kirsch T, Nagel G et al (2008) Spectral characteristics of the photocycle of channelrhodopsin-2 and its implication for channel function. J Mol Biol 375:686–694

    Article  PubMed  CAS  Google Scholar 

  • Bamberg E, Tittor J, Oesterhelt D (1993) Light-driven proton or chloride pumping by halorhodopsin. Proc Natl Acad Sci USA 90:639–643

    Article  PubMed  CAS  Google Scholar 

  • Berndt A, Yizhar O, Gunaydin LA et al (2009) Bi-stable neural state switches. Nat Neurosci 12:229–234

    Article  PubMed  CAS  Google Scholar 

  • Bernstein JG, Han X, Henninger MA et al (2008) Prosthetic systems for therapeutic optical activation and silencing of genetically-targeted neurons. Proc Soc Photo Opt Instrum Eng 6854:68540H

    PubMed  Google Scholar 

  • Bernstein JG, Boyden ES (2011) Optogenetic tools for analyzing the neural circuits of behavior. Trends Cogn Sci 15:592–600

    Article  PubMed  Google Scholar 

  • Bi A, Cui J, Ma YP et al (2006) Ectopic expression of a microbial-type rhodopsin restores visual responses in mice with photoreceptor degeneration. Neuron 50:23–33

    Article  PubMed  CAS  Google Scholar 

  • Boyden ES, Zhang F, Bamberg E et al (2005) Millisecond-timescale, genetically targeted optical control of neural activity. Nat Neurosci 8:1263–1268

    Article  PubMed  CAS  Google Scholar 

  • Busskamp V, Duebel J, Balya D et al (2010) Genetic reactivation of cone photoreceptors restores visual responses in retinitis pigmentosa. Science 329:413–417

    Article  PubMed  CAS  Google Scholar 

  • Cardin JA, Carlen M, Meletis K et al (2010) Targeted optogenetic stimulation and recording of neurons in vivo using cell-type-specific expression of Channelrhodopsin-2. Nat Protoc 5:247–254

    Article  PubMed  CAS  Google Scholar 

  • Cardin JA, Carlen M, Meletis K et al (2009) Driving fast-spiking cells induces gamma rhythm and controls sensory responses. Nature 459:663–667

    Article  PubMed  CAS  Google Scholar 

  • Carter ME, Adamantidis A, Ohtsu H et al (2009) Sleep homeostasis modulates hypocretin-mediated sleep-to-wake transitions. J Neurosci 29:10939–10949

    Article  PubMed  CAS  Google Scholar 

  • Carter ME, Yizhar O, Chikahisa S et al (2010) Tuning arousal with optogenetic modulation of locus coeruleus neurons. Nat Neurosci 13:1526–1533

    Article  PubMed  CAS  Google Scholar 

  • Carter M, Shieh JC (2010) Guide to research techniques in neuroscience. Elsevier/Academic, Amsterdam/Boston

    Google Scholar 

  • Cepko C (2010) Neuroscience. Seeing the light of day. Science 329:403–404

    Article  PubMed  CAS  Google Scholar 

  • Chow BY, Han X, Dobry AS et al (2010) High-performance genetically targetable optical neural silencing by light-driven proton pumps. Nature 463:98–102

    Article  PubMed  CAS  Google Scholar 

  • Ciocchi S, Herry C, Grenier F et al (2010) Encoding of conditioned fear in central amygdala inhibitory circuits. Nature 468:277–282

    Article  PubMed  CAS  Google Scholar 

  • Covington HE 3rd, Lobo MK, Maze I et al (2010) Antidepressant effect of optogenetic stimulation of the medial prefrontal cortex. J Neurosci 30:16082–16090

    Article  PubMed  CAS  Google Scholar 

  • Desai M, Kahn I, Knoblich U et al (2011) Mapping brain networks in awake mice using combined optical neural control and fMRI. J Neurophysiol 105:1393–1405

    Article  PubMed  CAS  Google Scholar 

  • Gong S, Doughty M, Harbaugh CR et al (2007) Targeting Cre recombinase to specific neuron populations with bacterial artificial chromosome constructs. J Neurosci 27:9817–9823

    Article  PubMed  CAS  Google Scholar 

  • Gradinaru V, Mogri M, Thompson KR et al (2009) Optical deconstruction of parkinsonian neural circuitry. Science 324:354–359

    Article  PubMed  CAS  Google Scholar 

  • Gradinaru V, Thompson KR, Deisseroth K (2008) eNpHR: a Natronomonas halorhodopsin enhanced for optogenetic applications. Brain Cell Biol 36:129–139

    Article  PubMed  Google Scholar 

  • Gradinaru V, Thompson KR, Zhang F et al (2007) Targeting and readout strategies for fast optical neural control in vitro and in vivo. J Neurosci 27:14231–14238

    Article  PubMed  CAS  Google Scholar 

  • Gradinaru V, Zhang F, Ramakrishnan C et al (2010) Molecular and cellular approaches for diversifying and extending optogenetics. Cell 141:154–165

    Article  PubMed  CAS  Google Scholar 

  • Gunaydin LA, Yizhar O, Berndt A et al (2010) Ultrafast optogenetic control. Nat Neurosci 13:387–392

    Article  PubMed  CAS  Google Scholar 

  • Han X, Boyden ES (2007) Multiple-color optical activation, silencing, and desynchronization of neural activity, with single-spike temporal resolution. PLoS One 2:e299

    Article  PubMed  Google Scholar 

  • Haubensak W, Kunwar PS, Cai H et al (2010) Genetic dissection of an amygdala microcircuit that gates conditioned fear. Nature 468:270–276

    Article  PubMed  CAS  Google Scholar 

  • Huber D, Petreanu L, Ghitani N et al (2008) Sparse optical microstimulation in barrel cortex drives learned behaviour in freely moving mice. Nature 451:61–64

    Article  PubMed  CAS  Google Scholar 

  • Hull C, Adesnik H, Scanziani M (2009) Neocortical disynaptic inhibition requires somatodendritic integration in interneurons. J Neurosci 29:8991–8995

    Article  PubMed  CAS  Google Scholar 

  • Kahn I, Desai M, Knoblich U et al (2011) Characterization of the functional MRI response temporal linearity via optical control of neocortical pyramidal neurons. J Neurosci 31:15086–15091

    Article  PubMed  CAS  Google Scholar 

  • Karnik SS, Gogonea C, Patil S et al (2003) Activation of G-protein-coupled receptors: a common molecular mechanism. Trends Endocrinol Metab 14:431–437

    Article  PubMed  CAS  Google Scholar 

  • Kim JM, Hwa J, Garriga P et al (2005) Light-driven activation of beta 2-adrenergic receptor signaling by a chimeric rhodopsin containing the beta 2-adrenergic receptor cytoplasmic loops. Biochemistry 44:2284–2292

    Article  PubMed  CAS  Google Scholar 

  • Kralj JM, Douglass AD, Hochbaum DR et al (2011) Optical recording of action potentials in mammalian neurons using a microbial rhodopsin. Nat Methods 9:90–95

    Article  PubMed  Google Scholar 

  • Kramer RH, Fortin DL, Trauner D (2009) New photochemical tools for controlling neuronal activity. Curr Opin Neurobiol 19:544–552

    Article  PubMed  CAS  Google Scholar 

  • Kravitz AV, Freeze BS, Parker PR et al (2010) Regulation of parkinsonian motor behaviours by optogenetic control of basal ganglia circuitry. Nature 466:622–626

    Article  PubMed  CAS  Google Scholar 

  • Lagali PS, Balya D, Awatramani GB et al (2008) Light-activated channels targeted to ON bipolar cells restore visual function in retinal degeneration. Nat Neurosci 11:667–675

    Article  PubMed  CAS  Google Scholar 

  • Lee JH, Durand R, Gradinaru V et al (2010) Global and local fMRI signals driven by neurons defined optogenetically by type and wiring. Nature 465:788–792

    Article  PubMed  CAS  Google Scholar 

  • Li X, Gutierrez DV, Hanson MG et al (2005) Fast noninvasive activation and inhibition of neural and network activity by vertebrate rhodopsin and green algae channelrhodopsin. Proc Natl Acad Sci USA 102:17816–17821

    Article  PubMed  CAS  Google Scholar 

  • Lin D, Boyle MP, Dollar P et al (2011) Functional identification of an aggression locus in the mouse hypothalamus. Nature 470:221–226

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Luo L, Callaway EM, Svoboda K (2008) Genetic dissection of neural circuits. Neuron 57:634–660

    Article  PubMed  CAS  Google Scholar 

  • Madisen L, Zwingman TA, Sunkin SM et al (2010) A robust and high-throughput Cre reporting and characterization system for the whole mouse brain. Nat Neurosci 13:133–140

    Article  PubMed  CAS  Google Scholar 

  • Nagel G, Szellas T, Huhn W et al (2003) Channelrhodopsin-2, a directly light-gated cation-selective membrane channel. Proc Natl Acad Sci USA 100:13940–13945

    Article  PubMed  CAS  Google Scholar 

  • Oh E, Maejima T, Liu C et al (2010) Substitution of 5-HT1A receptor signaling by a light-activated G protein-coupled receptor. J Biol Chem 285:30825–30836

    Article  PubMed  CAS  Google Scholar 

  • Osakada F, Mori T, Cetin AH et al (2011) New rabies virus variants for monitoring and manipulating activity and gene expression in defined neural circuits. Neuron 71:617–631

    Article  PubMed  CAS  Google Scholar 

  • Rickgauer JP, Tank DW (2009) Two-photon excitation of channelrhodopsin-2 at saturation. Proc Natl Acad Sci USA 106:15025–15030

    Article  PubMed  CAS  Google Scholar 

  • Sawadsaringkarn Y, Kimura H, Maezawa Y et al (2012) CMOS on-chip optoelectronic neural interface device with integrated light source for optogenetics. J Phys Conf Ser 352:012004

    Article  Google Scholar 

  • Schobert B, Lanyi JK (1982) Halorhodopsin is a light-driven chloride pump. J Biol Chem 257:10306–10313

    PubMed  CAS  Google Scholar 

  • Sohal VS, Zhang F, Yizhar O et al (2009) Parvalbumin neurons and gamma rhythms enhance cortical circuit performance. Nature 459:698–702

    Article  PubMed  CAS  Google Scholar 

  • Stuber GD (2010) Dissecting the neural circuitry of addiction and psychiatric disease with optogenetics. Neuropsychopharmacology 35:341–342

    Article  PubMed  Google Scholar 

  • Stuber GD, Hnasko TS, Britt JP et al (2010) Dopaminergic terminals in the nucleus accumbens but not the dorsal striatum corelease glutamate. J Neurosci 30:8229–8233

    Article  PubMed  CAS  Google Scholar 

  • Tecuapetla F, Patel JC, Xenias H et al (2010) Glutamatergic signaling by mesolimbic dopamine neurons in the nucleus accumbens. J Neurosci 30:7105–7110

    Article  PubMed  CAS  Google Scholar 

  • Tomita H, Sugano E, Fukazawa Y et al (2009) Visual properties of transgenic rats harboring the channelrhodopsin-2 gene regulated by the thy-1.2 promoter. PLoS One 4:e7679

    Article  PubMed  Google Scholar 

  • Tomita H, Sugano E, Isago H et al (2010) Channelrhodopsin-2 gene transduced into retinal ganglion cells restores functional vision in genetically blind rats. Exp Eye Res 90:429–436

    Article  PubMed  CAS  Google Scholar 

  • Tonnesen J, Sorensen AT, Deisseroth K et al (2009) Optogenetic control of epileptiform activity. Proc Natl Acad Sci USA 106:12162–12167

    Article  PubMed  CAS  Google Scholar 

  • Tsai HC, Zhang F, Adamantidis A et al (2009) Phasic firing in dopaminergic neurons is sufficient for behavioral conditioning. Science 324:1080–1084

    Article  PubMed  CAS  Google Scholar 

  • Wall NR, Wickersham IR, Cetin A et al (2010) Monosynaptic circuit tracing in vivo through Cre-dependent targeting and complementation of modified rabies virus. Proc Natl Acad Sci USA 107:21848–21853

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  Google Scholar 

  • Zhang F, Aravanis AM, Adamantidis A et al (2007a) Circuit-breakers: optical technologies for probing neural signals and systems. Nat Rev Neurosci 8:577–581

    Article  PubMed  CAS  Google Scholar 

  • Zhang F, Gradinaru V, Adamantidis AR et al (2010) Optogenetic interrogation of neural circuits: technology for probing mammalian brain structures. Nat Protoc 5:439–456

    Article  PubMed  CAS  Google Scholar 

  • Zhang F, Prigge M, Beyriere F et al (2008) Red-shifted optogenetic excitation: a tool for fast neural control derived from Volvox carteri. Nat Neurosci 11:631–633

    Article  PubMed  Google Scholar 

  • Zhang F, Wang LP, Boyden ES et al (2006) Channelrhodopsin-2 and optical control of excitable cells. Nat Methods 3:785–792

    Article  PubMed  CAS  Google Scholar 

  • Zhang F, Wang LP, Brauner M et al (2007b) Multimodal fast optical interrogation of neural circuitry. Nature 446:633–639

    Article  PubMed  CAS  Google Scholar 

  • Zhang Y, Ivanova E, Bi A et al (2009) Ectopic expression of multiple microbial rhodopsins restores ON and OFF light responses in retinas with photoreceptor degeneration. J Neurosci 29:9186–9196

    Article  PubMed  CAS  Google Scholar 

  • Zhao S, Cunha C, Zhang F et al (2008) Improved expression of halorhodopsin for light-induced silencing of neuronal activity. Brain Cell Biol 36:141–154

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

We thank all members of our laboratories for useful discussion and support. Fig. 8.1 was adopted from the front page of BioGARAGE, published on March 2012 by Leave a Nest Co., Ltd. The images in both figures were designed by Science Graphics Co., Ltd.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Shoji Komai .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2013 Springer

About this chapter

Cite this chapter

Cetin, A., Komai, S. (2013). Controlling Behavior Using Light to Excite and Silence Neuronal Activity. In: Ogawa, H., Oka, K. (eds) Methods in Neuroethological Research. Springer, Tokyo. https://doi.org/10.1007/978-4-431-54331-2_8

Download citation

Publish with us

Policies and ethics