Disruption of NMDAR-dependent burst firing by dopamine neurons provides selective assessment of phasic dopamine-dependent behavior
- Larry S. Zweifela,b,
- Jones G. Parkera,b,
- Collin J. Lobbc,
- Aundrea Rainwatera,b,
- Valerie Z. Walla,b,
- Jonathan P. Fadoka,b,
- Martin Darvasa,b,
- Min J. Kimd,
- Sheri J. Y. Mizumorid,
- Carlos A. Paladinic,
- Paul E. M. Phillipse,f and
- Richard D. Palmitera,b,1
- Departments of dPsychology,
- ePsychiatry and Behavioral Sciences,
- fPharmacology, and
- aBiochemistry and
- bHoward Hughes Medical Institute, University of Washington, Seattle, WA 98195; and
- cDepartment of Biology, University of Texas, San Antonio, TX 78249
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Edited by Richard L. Huganir, Johns Hopkins University School of Medicine, Baltimore, MD, and approved February 20, 2009 (received for review December 31, 2008)
Abstract
Midbrain dopamine (DA) neurons fire in 2 characteristic modes, tonic and phasic, which are thought to modulate distinct aspects of behavior. However, the inability to selectively disrupt these patterns of activity has hampered the precise definition of the function of these modes of signaling. Here, we addressed the role of phasic DA in learning and other DA-dependent behaviors by attenuating DA neuron burst firing and subsequent DA release, without altering tonic neural activity. Disruption of phasic DA was achieved by selective genetic inactivation of NMDA-type, ionotropic glutamate receptors in DA neurons. Disruption of phasic DA neuron activity impaired the acquisition of numerous conditioned behavioral responses, and dramatically attenuated learning about cues that predicted rewarding and aversive events while leaving many other DA-dependent behaviors unaffected.
Footnotes
- 1To whom correspondence should be addressed. E-mail: palmiter{at}u.washington.edu
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This Feature Article is part of a series identified by the Editorial Board as reporting findings of exceptional significance.
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Author contributions: L.S.Z. and R.D.P. designed research; L.S.Z., J.G.P., C.J.L., A.R., V.Z.W., J.P.F., and M.D. performed research; M.J.K., S.J.Y.M., C.A.P., P.E.M.P., and R.D.P. contributed new reagents/analytic tools; L.S.Z., J.G.P., A.R., J.P.F., M.D., and M.J.K. analyzed data; and L.S.Z. wrote the paper.
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The authors declare no conflict of interest.
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This article is a PNAS Direct Submission.
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See Commentary on page 7267.
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This article contains supporting information online at www.pnas.org/cgi/content/full/0813415106/DCSupplemental.
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Freely available online through the PNAS open access option.
