Disruption of NMDAR-dependent burst firing by dopamine neurons provides selective assessment of phasic dopamine-dependent behavior

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,...

Full description

Saved in:

Bibliographic Details
Published in:	Proceedings of the National Academy of Sciences - PNAS Vol. 106; no. 18; pp. 7281 - 7288
Main Authors:	Zweifel, Larry S, Parker, Jones G, Lobb, Collin J, Rainwater, Aundrea, Wall, Valerie Z, Fadok, Jonathan P, Darvas, Martin, Kim, Min J, Mizumori, Sheri J.Y, Paladini, Carlos A, Phillips, Paul E.M, Palmiter, Richard D
Format:	Journal Article
Language:	English
Published:	United States National Academy of Sciences 05-05-2009 National Acad Sciences
Series:	From the Cover
Subjects:	Animal behavior Animal cognition Animals Attention Behavior Behavioral neuroscience Biological Sciences Brain Cocaine Dopamine - metabolism Dopamine - physiology Drinking Electrodes Fear Genotypes Learning Maze Learning Mazes Mental stimulation Mesencephalon - cytology Mesencephalon - metabolism Mesencephalon - physiology Mice Mice, Knockout Neurons Neurons - metabolism Neurons - physiology Neurotransmitters Receptors, N-Methyl-D-Aspartate - genetics Receptors, N-Methyl-D-Aspartate - physiology Reward Signal transduction Training
Online Access:	Get full text
Tags:	Add Tag No Tags, Be the first to tag this record!

Description
Summary:	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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 This Feature Article is part of a series identified by the Editorial Board as reporting findings of exceptional significance. 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. Edited by Richard L. Huganir, Johns Hopkins University School of Medicine, Baltimore, MD, and approved February 20, 2009
ISSN:	0027-8424 1091-6490
DOI:	10.1073/pnas.0813415106