Home LiteratureArticle Details
PMID: 19389999 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S.

Phasic firing in dopaminergic neurons is sufficient for behavioral conditioning.

Science (New York, N.Y.) ·Vol. 324 ·No. 5930 ·2009-05-22 ·Pages 1080-4

Tsai HC, Zhang F, Adamantidis A, Stuber GD, Bonci A, de Lecea L, Deisseroth K

Abstract

Natural rewards and drugs of abuse can alter dopamine signaling, and ventral tegmental area (VTA) dopaminergic neurons are known to fire action potentials tonically or phasically under different behavioral conditions. However, without technology to control specific neurons with appropriate temporal precision in freely behaving mammals, the causal role of these action potential patterns in driving behavioral changes has been unclear. We used optogenetic tools to selectively stimulate VTA dopaminergic neuron action potential firing in freely behaving mammals. We found that phasic activation of these neurons was sufficient to drive behavioral conditioning and elicited dopamine transients with magnitudes not achieved by longer, lower-frequency spiking. These results demonstrate that phasic dopaminergic activity is sufficient to mediate mammalian behavioral conditioning.

MeSH Terms
Action Potentials Animals Behavior, Animal Channelrhodopsins Conditioning, Psychological Dopamine/metabolism Electrodes, Implanted Genetic Vectors Light Mice Mice, Transgenic Neurons/physiology Patch-Clamp Techniques Reward Transduction, Genetic Ventral Tegmental Area/cytology,physiology
Chemicals
Channelrhodopsins Dopamine
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Tsai Hsing-Chen
Neuroscience Program, W080 Clark Center, 318 Campus Drive West, Stanford University, Stanford, CA 94305, USA.
Zhang Feng
Adamantidis Antoine
Stuber Garret D
Bonci Antonello
de Lecea Luis
Deisseroth Karl
References (28)
28 references, click to expand
  1. Nicotinic acetylcholine receptors and nicotinic cholinergic mechanisms of the central nervous system.
    Annu Rev Pharmacol Toxicol. 2007;47:699-729 PMID: 17009926
  2. Neuronal systems underlying behaviors related to nicotine addiction: neural circuits and molecular genetics.
    J Neurosci. 2002 May 1;22(9):3338-41 PMID: 11978809
  3. Subsecond dopamine release promotes cocaine seeking.
    Nature. 2003 Apr 10;422(6932):614-8 PMID: 12687000
  4. Cocaine-conditioned place preference by dopamine-deficient mice is mediated by serotonin.
    J Neurosci. 2007 Nov 14;27(46):12484-8 PMID: 18003826
  5. Neurobiology of cocaine addiction: implications for new pharmacotherapy.
    Am J Addict. 2007 Mar-Apr;16(2):71-8 PMID: 17453607
  6. Dichotomous dopaminergic control of striatal synaptic plasticity.
    Science. 2008 Aug 8;321(5890):848-51 PMID: 18687967
  7. Dopamine, learning, and impulsivity: a biological account of attention-deficit/hyperactivity disorder.
    J Child Adolesc Psychopharmacol. 2005 Apr;15(2):160-79; discussion 157-9 PMID: 15910202
  8. Measuring reward with the conditioned place preference (CPP) paradigm: update of the last decade.
    Addict Biol. 2007 Sep;12(3-4):227-462 PMID: 17678505
  9. Channelrhodopsin-2, a directly light-gated cation-selective membrane channel.
    Proc Natl Acad Sci U S A. 2003 Nov 25;100(24):13940-5 PMID: 14615590
  10. The mesolimbic dopamine reward circuit in depression.
    Biol Psychiatry. 2006 Jun 15;59(12):1151-9 PMID: 16566899
  11. Reward-predictive cues enhance excitatory synaptic strength onto midbrain dopamine neurons.
    Science. 2008 Sep 19;321(5896):1690-2 PMID: 18802002
  12. Dopamine, learning and motivation.
    Nat Rev Neurosci. 2004 Jun;5(6):483-94 PMID: 15152198
  13. Altered motivation and learning following opiate withdrawal: evidence for prolonged dysregulation of reward processing.
    Neuropsychopharmacology. 2003 May;28(5):865-71 PMID: 12736632
  14. Millisecond-timescale, genetically targeted optical control of neural activity.
    Nat Neurosci. 2005 Sep;8(9):1263-8 PMID: 16116447
  15. A FLEX switch targets Channelrhodopsin-2 to multiple cell types for imaging and long-range circuit mapping.
    J Neurosci. 2008 Jul 9;28(28):7025-30 PMID: 18614669
  16. Multiple dopamine functions at different time courses.
    Annu Rev Neurosci. 2007;30:259-88 PMID: 17600522
  17. Habits, rituals, and the evaluative brain.
    Annu Rev Neurosci. 2008;31:359-87 PMID: 18558860
  18. Regulation of firing of dopaminergic neurons and control of goal-directed behaviors.
    Trends Neurosci. 2007 May;30(5):220-7 PMID: 17400299
  19. Repeated cocaine exposure in vivo facilitates LTP induction in midbrain dopamine neurons.
    Nature. 2005 Oct 13;437(7061):1027-31 PMID: 16222299
  20. Firing properties of dopamine neurons in freely moving dopamine-deficient mice: effects of dopamine receptor activation and anesthesia.
    Proc Natl Acad Sci U S A. 2004 Sep 7;101(36):13329-34 PMID: 15317940
  21. Reward without dopamine.
    J Neurosci. 2003 Nov 26;23(34):10827-31 PMID: 14645475
  22. Uniform inhibition of dopamine neurons in the ventral tegmental area by aversive stimuli.
    Science. 2004 Mar 26;303(5666):2040-2 PMID: 15044807
  23. Neural substrates of awakening probed with optogenetic control of hypocretin neurons.
    Nature. 2007 Nov 15;450(7168):420-4 PMID: 17943086
  24. Neural systems of reinforcement for drug addiction: from actions to habits to compulsion.
    Nat Neurosci. 2005 Nov;8(11):1481-9 PMID: 16251991
  25. Dopamine neuron systems in the brain: an update.
    Trends Neurosci. 2007 May;30(5):194-202 PMID: 17408759
  26. Drug abuse: hedonic homeostatic dysregulation.
    Science. 1997 Oct 3;278(5335):52-8 PMID: 9311926
  27. Multimodal fast optical interrogation of neural circuitry.
    Nature. 2007 Apr 5;446(7136):633-9 PMID: 17410168
  28. The neural basis of drug craving: an incentive-sensitization theory of addiction.
    Brain Res Brain Res Rev. 1993 Sep-Dec;18(3):247-91 PMID: 8401595
Article Info
Journal
Science (New York, N.Y.)
Abbr.
Science
ISSN
1095-9203
Published
2009-05-22
Epub
2009-00-23
Pages
1080-4
Language
English
Region
United States
NLM ID
0404511
PMCID
PMC5262197
Subset
IM
Grants
NINDS NIH HHS · K99 NS065009 · United States
NINDS NIH HHS · K99 NS065009-02 · United States
NIDA NIH HHS · R01 DA021880 · United States
NIMH NIH HHS · R01 MH087592 · United States
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]