Optical Control of Neuronal Activity

Luis de Lecea, Stanford University School of Medicine, Stanford, California, USA
Matthew E Carter, Stanford University School of Medicine, Stanford, California, USA

Published online: April 2011

DOI: 10.1002/9780470015902.a0022503

Abstract

Optogenetics has become an invaluable method to establish causal relationships between the activity of genetically defined neuronal circuits and behaviour. Channelrhodopsin 2 is a light‐activated channel that, when introduced in neurons allows temporally precise control of the activity of genetically identified neuronal networks. Conversely, halorhodopsins are light sensitive ion pumps that allow us to reversibly inhibit neuronal transmission with single action potential resolution. These optical tools offer new approaches to deconstruct neuronal circuits in freely moving animals. New variants of light‐activated channels and pumps offer a menu of optogenetic tools that allow us to determine functional connectivities and dynamic properties of brain networks. The development of optogenetics has profound implications in our understanding of brain organisation and mechanisms of neuropsychiatric disease.

Key Concepts:

  • Introduction of Channelrhodopsin 2 in neurons allows millisecond optical control of genetically identified neurons.

  • Different mutants of ChR2 show different kinetic properties, spectral sensitivity.

  • Different gene delivery methods allow dissection of neuronal circuits even in the absence of genetic markers and in multiple model organisms.

  • Combination of optogenetics with gene deficiencies and imaging systems will allow significant improvements in our understanding of circuit dynamics and mechanisms of disease.

Keywords: optogenetics; Channelrhodopsin 2; halorhodopsin

Figure 1.

Optogenetic probes and the manipulation of neural circuits. (a) Probes that depolarise the membrane are nonselective cation channels that open in response to blue light. Probes that hyperpolarise the membrane are chloride or proton pumps that open in response to yellow light. (b) Optogenetic probes can be expressed in specific populations of neurons in the brain and stimulated with implantable fiber optic cables.
close

References

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

Andrasfalvy BK, Zemelman BV, Tang J et al. (2010) Two‐photon single‐cell optogenetic control of neuronal activity by sculpted light. Proceedings of the National Academy of Sciences of the USA 107: 11981–11986.

Bamann C, Gueta R, Kleinlogel S et al. (2010) Structural guidance of the photocycle of channelrhodopsin‐2 by an interhelical hydrogen bond. Biochemistry 49: 267–278.

Bamann C, Kirsch T, Nagel G et al. (2008) Spectral characteristics of the photocycle of channelrhodopsin‐2 and its implication for channel function. Journal of Molecular Biology 375: 686–694.

Berndt A, Yizhar O, Gunaydin LA et al. (2009) Bi‐stable neural state switches. Nature Neuroscience 12: 229–234.

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.

Crick F and Koch C (1998) Consciousness and neuroscience. Cerebral Cortex 8: 97–107.

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

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

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

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

Johansen JP, Tarpley JW, LeDoux JE and Blair HT (2010) Neural substrates for expectation‐modulated fear learning in the amygdala and periaqueductal gray. Nature Neuroscience 13(8): 979–986.

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.

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.

Lima SQ, Hromadka T, Znamenskiy P et al. (2009) PINP: a new method of tagging neuronal populations for identification during in vivo electrophysiological recording. PLoS ONE 4: e6099.

Lin JY (2010) A user's guide to channelrhodopsin variants: features, limitations and future developments. Experimental Physiology 96(1): 19–25.

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

Nagel G, Brauner M, Liewald JF et al. (2005) Light activation of channelrhodopsin‐2 in excitable cells of Caenorhabditis elegans triggers rapid behavioral responses. Current Biology 15: 2279–2284.

Nagel G, Szellas T, Huhn W et al. (2003) Channelrhodopsin‐2, a directly light‐gated cation‐selective membrane channel. Proceedings of the National Academy of Sciences of the USA 100: 13940–13945.

Petreanu L, Huber D, Sobczyk A et al. (2007) Channelrhodopsin‐2‐assisted circuit mapping of long‐range callosal projections. Nature Neuroscience 10: 663–668.

Petreanu L, Mao T, Sternson SM et al. (2009) The subcellular organization of neocortical excitatory connections. Nature 457: 1142–1145.

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

Toni N, Laplagne DA, Zhao C et al. (2008) Neurons born in the adult dentate gyrus form functional synapses with target cells. Nature Neuroscience 11: 901–907.

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

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

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

Zhang J, Laiwalla F, Kim JA et al. (2009a) A microelectrode array incorporating an optical waveguide device for stimulation and spatiotemporal electrical recording of neural activity. Conference Proceedings – IEEE Engineering in Medicine and Biology Society 2009: 2046–2049.

Zhang J, Laiwalla F, Kim JA et al. (2009b) Integrated device for optical stimulation and spatiotemporal electrical recording of neural activity in light‐sensitized brain tissue. Journal of Neural Engineering 6: 55007.

Zhang YP, Holbro N and Oertner TG (2008b) Optical induction of plasticity at single synapses reveals input‐specific accumulation of alphaCaMKII. Proceedings of the National Academy of Sciences of the USA 105: 12039–12044.

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

Further Reading

Adamantidis A, Carter MC and de Lecea L (2010) Optogenetic deconstruction of sleep‐wake circuitry in the brain. Frontiers in Molecular Neuroscience 2: 31.

Miesenbock G (2009) The optogenetic catechism. Science 326: 395–399.

Miesenbock G and Kevrekidis IG (2005) Optical imaging and control of genetically designated neurons in functioning circuits. Annual Review of Neuroscience 28: 533–563.

Palmer HS (2010) Optogenetic fMRI sheds light on the neural basis of the BOLD signal. Journal of Neurophysiology 104: 1838–1840.

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

Related Sub-Topics:

Neurobiology of Disease | Organisation of the Nervous System | Neural Networks and Behaviour | Neurons
Contact Editor close
Submit a note to the editor about this article by filling in the form below.

* Required Field

Article Title: Optical Control of Neuronal Activity
 
How to Cite close
de Lecea, Luis, and Carter, Matthew E(Apr 2011) Optical Control of Neuronal Activity. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0022503]