NMDA receptors in dopaminergic neurons are crucial for habit learning

Lei Wang, Fei Li, Dong Wang, Kun Xie, Deheng Wang, Xiaoming Shen, Joseph Zhuo Tsien

Research output: Contribution to journalArticle

80 Scopus citations

Abstract

Dopamine is crucial for habit learning. Activities of midbrain dopaminergic neurons are regulated by the cortical and subcortical signals among which glutamatergic afferents provide excitatory inputs. Cognitive implications of glutamatergic afferents in regulating and engaging dopamine signals during habit learning, however, remain unclear. Here, we show that mice with dopaminergic neuron-specific NMDAR1 deletion are impaired in a variety of habit-learning tasks, while normal in some other dopamine-modulated functions such as locomotor activities, goal-directed learning, and spatial reference memories. In vivo neural recording revealed that dopaminergic neurons in these mutant mice could still develop the cue-reward association responses; however, their conditioned response robustness was drastically blunted. Our results suggest that integration of glutamatergic inputs to DA neurons by NMDA receptors, likely by regulating associative activity patterns, is a crucial part of the cellular mechanism underpinning habit learning. Video Abstract:

Original languageEnglish (US)
Pages (from-to)1055-1066
Number of pages12
JournalNeuron
Volume72
Issue number6
DOIs
StatePublished - Dec 22 2011

ASJC Scopus subject areas

  • Neuroscience(all)

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    Wang, L., Li, F., Wang, D., Xie, K., Wang, D., Shen, X., & Tsien, J. Z. (2011). NMDA receptors in dopaminergic neurons are crucial for habit learning. Neuron, 72(6), 1055-1066. https://doi.org/10.1016/j.neuron.2011.10.019