TY - JOUR
T1 - NMDA receptors in dopaminergic neurons are crucial for habit learning
AU - Wang, Lei
AU - Li, Fei
AU - Wang, Dong
AU - Xie, Kun
AU - Wang, Deheng
AU - Shen, Xiaoming
AU - Tsien, Joseph Zhuo
N1 - Funding Information:
We thank Fengying Huang and Brianna Klein for technical assistance. This work was supported by funds from NIMH, NIA, and Georgia Research Alliance (all to J.Z.T.). L.P.W., F.L., X.S., and J.Z.T. conceived and designed the experiments. L.P.W., F.L., D.W., K.X., and D.H.W. performed the experiments. L.P.W., F.L., D.W., K.X., and J.Z.T. analyzed the data. L.P.W., F.L., X.S., and J.Z.T. contributed reagents/materials/analysis tools. L.P.W., F.L., K.X., and J.Z.T. wrote the paper. All experiments involving animals were performed according to procedures approved by the Georgia Health Sciences University IACUC review board.
PY - 2011/12/22
Y1 - 2011/12/22
N2 - 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:
AB - 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:
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U2 - 10.1016/j.neuron.2011.10.019
DO - 10.1016/j.neuron.2011.10.019
M3 - Article
C2 - 22196339
AN - SCOPUS:84155183278
SN - 0896-6273
VL - 72
SP - 1055
EP - 1066
JO - Neuron
JF - Neuron
IS - 6
ER -