Wiltgen Brian J, Law Matthew, Ostlund Sean, Mayford Mark, Balleine Bernard W
Department of Psychology and the Brain Research Institute, University of California, Los Angeles, CA 90095, USA.
Eur J Neurosci. 2007 Apr;25(8):2491-7. doi: 10.1111/j.1460-9568.2007.05487.x.
Pavlovian cues associated with reward exert a powerful motivational influence on the performance of goal-directed actions. This motivational process depends critically on the ventral striatum, although little is known about the cellular and molecular mechanisms that mediate it. In the current experiments we examined the role of calcium calmodulin-dependent kinase II (CaMKII) by using transgenic mice that express a constitutively active form of this kinase. We found that controlled expression of active CaMKII in the striatum did not affect learning but did impair the motivation of goal-directed actions by Pavlovian cues associated with reward. Mutant mice learned to lever press for reward, remained sensitive to outcome devaluation and contingency degradation manipulations, and were able to acquire Pavlovian responses to cues paired with reward. However, Pavlovian cues were completely unable to motivate lever pressing in mutant mice. This was true even in mice trained with the CaMKII transgene turned off and then tested with it turned on. We were also able to suppress transgene expression in impaired mutants and fully restore the motivational effects of reward cues in these animals. Therefore, the current experiments demonstrate that normal CaMKII activity in the striatum is essential for the motivational effects of reward cues on goal-directed actions.
与奖励相关的巴甫洛夫线索对目标导向行为的表现施加强大的动机影响。这一动机过程严重依赖腹侧纹状体，尽管对介导该过程的细胞和分子机制知之甚少。在当前实验中，我们通过使用表达该激酶组成型活性形式的转基因小鼠来研究钙调蛋白依赖性激酶II（CaMKII）的作用。我们发现，纹状体中活性CaMKII的可控表达不影响学习，但确实损害了与奖励相关的巴甫洛夫线索对目标导向行为的动机。突变小鼠学会了按压杠杆以获取奖励，对结果贬值和偶然性降解操作仍保持敏感，并且能够对与奖励配对的线索产生巴甫洛夫反应。然而，巴甫洛夫线索完全无法激发突变小鼠按压杠杆。即使在关闭CaMKII转基因进行训练然后打开转基因进行测试的小鼠中也是如此。我们还能够在受损的突变体中抑制转基因表达，并完全恢复这些动物中奖励线索的动机效应。因此，当前实验表明，纹状体中正常的CaMKII活性对于奖励线索对目标导向行为的动机效应至关重要。
