Inverted-U dopamine D1 receptor actions on prefrontal neurons engaged in working memory

被引:760
作者
Vijayraghavan, Susheel
Wang, Min
Birnbaum, Shari G.
Williams, Graham V.
Arnsten, Amy F. T.
机构
[1] Yale Univ, Sch Med, Dept Neurobiol, New Haven, CT 06520 USA
[2] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT 06511 USA
关键词
D O I
10.1038/nn1846
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Dopamine (DA) D1 receptor (D1R) stimulation in prefrontal cortex (PFC) produces an 'inverted-U' dose-response, whereby either too little or too much D1R stimulation impairs spatial working memory. This response has been observed across species, including genetic linkages with human cognitive abilities, PFC activation states and DA synthesis. The cellular basis for the inverted U has long been sought, with in vitro intracellular recordings supporting a variety of potential mechanisms. The current study demonstrates that the D1R agonist inverted-U response can be observed in PFC neurons of behaving monkeys: low levels of D1R stimulation enhance spatial tuning by suppressing responses to nonpreferred directions, whereas high levels reduce delay-related firing for all directions, eroding tuning. These sculpting actions of D1R stimulation are mediated in monkeys and rats by cyclic AMP intracellular signaling. The evidence for an inverted U at the cellular level in behaving animals promises to bridge in vitro molecular analyses with human cognitive experience.
引用
收藏
页码:376 / 384
页数:9
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