Brain and Behavior Discovery Institute and Department of Neurology, Georgia Health Sciences University, Augusta, GA 30912, USA.
Neuron. 2011 Dec 22;72(6):1055-66. doi: 10.1016/j.neuron.2011.10.019.
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.
多巴胺对于习惯学习至关重要。中脑多巴胺能神经元的活动受到皮质和皮质下信号的调节，其中谷氨酸能传入提供兴奋性输入。然而，在习惯学习过程中调节和参与多巴胺信号的谷氨酸能传入的认知意义尚不清楚。在这里，我们表明，多巴胺能神经元特异性 NMDAR1 缺失的小鼠在各种习惯学习任务中受损，而在其他一些多巴胺调节的功能中正常，如运动活动、目标导向学习和空间参照记忆。体内神经记录显示，这些突变小鼠的多巴胺能神经元仍然可以发展出线索-奖励关联反应；然而，它们的条件反应稳健性大大降低。我们的结果表明，NMDA 受体对 DA 神经元的谷氨酸能输入的整合，可能通过调节关联活动模式，是习惯学习的细胞机制的重要组成部分。
