Howard Hughes Medical Institute, and Department of Neurobiology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Proc Natl Acad Sci U S A. 2013 Feb 26;110(9):3579-84. doi: 10.1073/pnas.1221236110. Epub 2013 Feb 11.
To investigate mechanisms by which reward modulates target selection, we studied the behavioral effects of perturbing dopaminergic activity within the frontal eye field (FEF) of monkeys performing a saccadic choice task and simulated the effects using a plausible cortical network. We found that manipulation of FEF activity either by blocking D1 receptors (D1Rs) or by stimulating D2 receptors (D2Rs) increased the tendency to choose targets in the response field of the affected site. However, the D1R manipulation decreased the tendency to repeat choices on subsequent trials, whereas the D2R manipulation increased that tendency. Moreover, the amount of shift in target selection resulting from the two manipulations correlated in opposite ways with the baseline stochasticity of choice behavior. Our network simulation results suggest that D1Rs influence target selection mainly through their effects on the strength of inputs to the FEF and on recurrent connectivity, whereas D2Rs influence the excitability of FEF output neurons. Altogether, these results reveal dissociable dopaminergic mechanisms influencing target selection and suggest how reward can influence adaptive choice behavior via prefrontal dopamine.
为了探究奖赏调节目标选择的机制,我们研究了在猴子执行扫视选择任务时干扰额眼区(FEF)多巴胺能活动的行为效应,并使用一个合理的皮质网络模拟了这些效应。我们发现,通过阻断 D1 受体(D1Rs)或刺激 D2 受体(D2Rs)来操纵 FEF 活动,都会增加选择受影响部位反应场中目标的倾向。然而,D1R 操作会降低后续试验中重复选择的倾向,而 D2R 操作则会增加这种倾向。此外,两种操作导致的目标选择转移量与选择行为的基线随机性呈相反方式相关。我们的网络模拟结果表明,D1Rs 主要通过其对 FEF 输入强度和递归连接的影响来影响目标选择,而 D2Rs 则影响 FEF 输出神经元的兴奋性。总之,这些结果揭示了影响目标选择的分离多巴胺能机制,并表明奖励如何通过前额叶多巴胺影响适应性选择行为。