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

Larry S. Zweifel, Jones Griffith Parker, Collin J. Lobb, Aundrea Rainwater, Valeriez Wall, Jonathan P. Fadok, Martin Darvas, Min J. Kim, Sheri J.Y. Mizumori, Carlos A. Paladini, Paul E.M. Phillips, Richard D. Palmiter

Research output: Contribution to journalArticlepeer-review

275 Scopus citations

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, iono- tropic 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.

Original languageEnglish (US)
Pages (from-to)7281-7288
Number of pages8
JournalProceedings of the National Academy of Sciences of the United States of America
Volume106
Issue number18
DOIs
StatePublished - May 5 2009

Keywords

  • Cue-dependent learning
  • Electrophysiology cyclic voltammetry
  • Mouse behavior

ASJC Scopus subject areas

  • General

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