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
-
Nicotinic acetylcholine receptors and nicotinic cholinergic mechanisms of the central nervous system.
Annu Rev Pharmacol Toxicol. 2007;47:699-729
PMID: 17009926
-
Neuronal systems underlying behaviors related to nicotine addiction: neural circuits and molecular genetics.
J Neurosci. 2002 May 1;22(9):3338-41
PMID: 11978809
-
Subsecond dopamine release promotes cocaine seeking.
Nature. 2003 Apr 10;422(6932):614-8
PMID: 12687000
-
Cocaine-conditioned place preference by dopamine-deficient mice is mediated by serotonin.
J Neurosci. 2007 Nov 14;27(46):12484-8
PMID: 18003826
-
Neurobiology of cocaine addiction: implications for new pharmacotherapy.
Am J Addict. 2007 Mar-Apr;16(2):71-8
PMID: 17453607
-
Dichotomous dopaminergic control of striatal synaptic plasticity.
Science. 2008 Aug 8;321(5890):848-51
PMID: 18687967
-
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
-
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
-
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
-
The mesolimbic dopamine reward circuit in depression.
Biol Psychiatry. 2006 Jun 15;59(12):1151-9
PMID: 16566899
-
Reward-predictive cues enhance excitatory synaptic strength onto midbrain dopamine neurons.
Science. 2008 Sep 19;321(5896):1690-2
PMID: 18802002
-
Dopamine, learning and motivation.
Nat Rev Neurosci. 2004 Jun;5(6):483-94
PMID: 15152198
-
Altered motivation and learning following opiate withdrawal: evidence for prolonged dysregulation of reward processing.
Neuropsychopharmacology. 2003 May;28(5):865-71
PMID: 12736632
-
Millisecond-timescale, genetically targeted optical control of neural activity.
Nat Neurosci. 2005 Sep;8(9):1263-8
PMID: 16116447
-
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
-
Multiple dopamine functions at different time courses.
Annu Rev Neurosci. 2007;30:259-88
PMID: 17600522
-
Habits, rituals, and the evaluative brain.
Annu Rev Neurosci. 2008;31:359-87
PMID: 18558860
-
Regulation of firing of dopaminergic neurons and control of goal-directed behaviors.
Trends Neurosci. 2007 May;30(5):220-7
PMID: 17400299
-
Repeated cocaine exposure in vivo facilitates LTP induction in midbrain dopamine neurons.
Nature. 2005 Oct 13;437(7061):1027-31
PMID: 16222299
-
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
-
Reward without dopamine.
J Neurosci. 2003 Nov 26;23(34):10827-31
PMID: 14645475
-
Uniform inhibition of dopamine neurons in the ventral tegmental area by aversive stimuli.
Science. 2004 Mar 26;303(5666):2040-2
PMID: 15044807
-
Neural substrates of awakening probed with optogenetic control of hypocretin neurons.
Nature. 2007 Nov 15;450(7168):420-4
PMID: 17943086
-
Neural systems of reinforcement for drug addiction: from actions to habits to compulsion.
Nat Neurosci. 2005 Nov;8(11):1481-9
PMID: 16251991
-
Dopamine neuron systems in the brain: an update.
Trends Neurosci. 2007 May;30(5):194-202
PMID: 17408759
-
Drug abuse: hedonic homeostatic dysregulation.
Science. 1997 Oct 3;278(5335):52-8
PMID: 9311926
-
Multimodal fast optical interrogation of neural circuitry.
Nature. 2007 Apr 5;446(7136):633-9
PMID: 17410168
-
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