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Originally published in Science Express on 23 April 2009
Science 22 May 2009:
Vol. 324. no. 5930, pp. 1080 - 1084
DOI: 10.1126/science.1168878

Reports

Phasic Firing in Dopaminergic Neurons Is Sufficient for Behavioral Conditioning

Hsing-Chen Tsai,1,2,* Feng Zhang,2,* Antoine Adamantidis,3 Garret D. Stuber,4 Antonello Bonci,4 Luis de Lecea,3 Karl Deisseroth2,3,{dagger}

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.

1 Neuroscience Program, W080 Clark Center, 318 Campus Drive West, Stanford University, Stanford, CA 94305, USA.
2 Department of Bioengineering, W083 Clark Center, 318 Campus Drive West, Stanford University, Stanford, CA 94305, USA.
3 Department of Psychiatry and Behavioral Sciences, W083 Clark Center, 318 Campus Drive West, Stanford University, Stanford, CA 94305, USA.
4 Ernest Gallo Clinic and Research Center, Department of Neurology, Wheeler Center for the Neurobiology of Drug Addiction, University of California San Francisco, San Francisco, CA 94158, USA.

* These authors contributed equally to this work.

{dagger} To whom correspondence should be addressed. E-mail: deissero{at}stanford.edu

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