title: NMDA receptors in dopaminergic neurons are crucial for habit learning.
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.
authors.affiliation: Brain and Behavior Discovery Institute and Department of Neurology, Georgia Health Sciences University, Augusta, GA 30912, USA.
authors.forename: Lei Phillip
authors.initials: LP
authors.lastname: Wang
authors.forename: Fei
authors.initials: F
authors.lastname: Li
authors.forename: Dong
authors.initials: D
authors.lastname: Wang
authors.forename: Kun
authors.initials: K
authors.lastname: Xie
authors.forename: Deheng
authors.initials: D
authors.lastname: Wang
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Shen
authors.forename: Joe Z
authors.initials: JZ
authors.lastname: Tsien
mesh_terms: D000818:Animals; D059290:Dopaminergic Neurons / Q000502:physiology*; D006184:Habits; D007858:Learning / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011597:Psychomotor Performance / Q000502:physiology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology*
chemical_list: D016194:Receptors, N-Methyl-D-Aspartate