Klanker Marianne, Fellinger Lisanne, Feenstra Matthijs, Willuhn Ingo, Denys Damiaan
Netherlands Institute for Neuroscience, Institute of the Royal Netherlands Academy of Arts and Sciences, Meibergdreef 47, 1105 BA Amsterdam, The Netherlands; Department of Psychiatry, Academic Medical Center, University of Amsterdam, Postbus 22660, 1100 DD Amsterdam, The Netherlands.
Netherlands Institute for Neuroscience, Institute of the Royal Netherlands Academy of Arts and Sciences, Meibergdreef 47, 1105 BA Amsterdam, The Netherlands.
Neuroscience. 2017 Mar 14;345:110-123. doi: 10.1016/j.neuroscience.2016.05.011. Epub 2016 May 13.
Striatal dopamine (DA) plays a central role in reward-related learning and behavioral adaptation to changing environments. Recent studies suggest that rather than being broadcast as a uniform signal throughout the entire region, DA release dynamics diverge between different striatal regions. In a previous study, we showed that phasic DA release patterns in the ventromedial striatum (VMS) rapidly adapt during reversal learning. However, it is unknown how DA dynamics in the dorsolateral striatum (DLS) are modulated during such adaptive behavior. Here, we used fast-scan cyclic voltammetry to measure phasic DA release in the DLS during spatial reversal learning. In the DLS, we observed minor DA release after the onset of a visual cue signaling reward availability, followed by more pronounced DA release during more proximal reward cues (e.g., lever extension) and execution of the operant response (i.e., lever press), both in rewarded and non-rewarded trials. These release dynamics (minor DA after onset of the predictive visual cue, prominent DA during the operant response) did not change significantly during or following a reversal of response-reward contingencies. Notably, the DA increase to the lever press did not reflect a general signal related to the initiation of any motivated motor response, as we did not observe DA release when rats initiated nose pokes into the food receptacle during inter-trial intervals. This suggests that DA release in the DLS occurs selectively during the initiation and execution of a learned operant response. Together with our previous results obtained in the VMS, these findings reveal distinct phasic DA release patterns during adaptation of established behavior in DLS and VMS. The VMS DA signal, which is highly sensitive to reversal of response-reward contingences, may provide a teaching signal to guide reward-related learning and facilitate behavioral adaptation, whereas DLS DA may reflect a 'response execution signal' largely independent of outcome, that may be involved in initiation and energizing of operant behavior.
纹状体多巴胺（DA）在与奖励相关的学习以及对不断变化的环境的行为适应中起着核心作用。最近的研究表明，DA的释放动态并非在整个区域以统一信号进行传播，而是在不同的纹状体区域有所不同。在之前的一项研究中，我们表明腹内侧纹状体（VMS）中的相位性DA释放模式在反转学习过程中会迅速适应。然而，在这种适应性行为过程中背外侧纹状体（DLS）中的DA动态如何被调节尚不清楚。在这里，我们使用快速扫描循环伏安法来测量空间反转学习期间DLS中的相位性DA释放。在DLS中，我们观察到在指示奖励可用性的视觉线索出现后有少量DA释放，随后在更接近奖励的线索（例如杠杆伸展）以及操作性反应（即杠杆按压）执行期间，无论是在有奖励还是无奖励的试验中，都有更明显的DA释放。这些释放动态（预测性视觉线索出现后少量DA，操作性反应期间大量DA）在反应 - 奖励偶联反转期间或之后没有显著变化。值得注意的是，杠杆按压引起的DA增加并不反映与任何有动机的运动反应启动相关的一般信号，因为在试验间隔期间当大鼠开始将鼻子伸进食物容器时我们没有观察到DA释放。这表明DLS中的DA释放在习得的操作性反应的启动和执行过程中选择性地发生。与我们之前在VMS中获得的结果一起，这些发现揭示了在DLS和VMS中既定行为适应过程中不同的相位性DA释放模式。对反应 - 奖励偶联反转高度敏感的VMS DA信号可能提供一个教学信号来指导与奖励相关的学习并促进行为适应，而DLS DA可能反映一个很大程度上独立于结果的“反应执行信号”，其可能参与操作性行为的启动和激发。
