Contributions of striatal dopamine signaling to the modulation of cognitive flexibility.
Contributions of striatal dopamine signaling to the modulation of cognitive flexibility.
复制标题
DOI：
10.1016/j.biopsych.2010.09.033
复制
发表时间：
2011-04-01
影响因子：
10.6
通讯作者：
Palmiter, Richard D.
中科院分区：
文献类型：
--
作者：
Darvas, Martin;Palmiter, Richard D.
虽然认知灵活性是由前额叶皮层的不同区域介导的，但帕金森病患者的证据表明纹状体多巴胺（DA）信号的额外参与。由于背侧和腹侧纹状体都接受前额叶皮质的投射，目前还不清楚DA信号是否需要这两个区域之一或两者的认知灵活性。认知灵活性与水U型迷宫范式中，小鼠必须从最初获得的逃避策略，以一种新的策略或扭转最初学习的策略。我们测试了具有条件失活酪氨酸羟化酶基因的小鼠，这些基因可以被Cre重组酶激活。通过区域特异性病毒基因治疗，我们选择性地将DA信号限制在背侧或腹侧纹状体。限制DA信号的腹侧纹状体并没有损害学习的初始策略或反向学习，但强烈破坏的策略转移。相比之下，DA信号仅限于背侧纹状体的小鼠对初始策略、反向学习和策略转移的学习效果良好。背侧和腹侧纹状体中的多巴胺信号足以进行反向学习，而背侧纹状体中只有DA信号足以进行更苛刻的策略转换任务。
Although cognitive flexibility is mediated by different areas of the prefrontal cortex, evidence from patients with Parkinson’s disease suggests an additional involvement of striatal dopamine (DA) signaling. Because both dorsal and ventral striatum receive prefrontal cortex projections, it is unclear whether DA signaling to either one or both of these regions is required for cognitive flexibility. Cognitive flexibility was examined with a water U-maze paradigm in which mice had to shift from an initially acquired escape strategy to a new strategy or to reverse the initially learned strategy. We tested mice with conditionally inactive tyrosine hydroxylase genes that can be activated by Cre recombinase. With region-specific viral gene therapy we selectively restricted DA signaling to either dorsal or ventral striatum. Restricting DA signaling to the ventral striatum did not impair learning of the initial strategy or reversal-learning but strongly disrupted strategy-shifting. In contrast, mice with DA signaling restricted to the dorsal striatum had intact learning of the initial strategy, reversal-learning, and strategy-shifting. Dopamine signaling in both dorsal and ventral striatum is sufficient for reversal-learning, whereas only DA signaling in the dorsal striatum is sufficient for the more demanding strategy-shifting task.
登录
查看更多内容
影响因子：
25
作者：
Goto, Y;Grace, AA
通讯作者：
Grace, AA
影响因子：
5.3
作者：
Floresco, SB;Ghods-Sharifi, S;Magyar, O
通讯作者：
Magyar, O
影响因子：
1.9
作者：
Stefani, MR;Groth, K;Moghaddam, B
通讯作者：
Moghaddam, B
影响因子：
5.3
作者：
Reynolds, SM;Zahm, DS
通讯作者：
Zahm, DS
影响因子：
15.9
作者：
Brown, VJ;Bowman, EM
通讯作者：
Bowman, EM