Jenni Nicole L, Larkin Joshua D, Floresco Stan B
Department of Psychology and Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver, British Columbia V6T 1Z4, Canada.
Department of Psychology and Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver, British Columbia V6T 1Z4, Canada
J Neurosci. 2017 Jun 28;37(26):6200-6213. doi: 10.1523/JNEUROSCI.0030-17.2017. Epub 2017 May 25.
Mesocortical dopamine (DA) regulates a variety of cognitive functions via actions on D and/or D receptors. For example, risk/reward decision making is modulated differentially by these two receptors within the prefrontal cortex (PFC), with D receptors enabling flexible decision making and D receptors promoting persistence in choice biases. However, it is unclear how DA mediates opposing patterns of behavior by acting on different receptors within the same terminal region. We explored the possibility that DA may act on separate networks of PFC neurons that are modulated by D or D receptors and in turn interface with divergent downstream structures such as the basolateral amygdala (BLA) or nucleus accumbens (NAc). Decision making was assessed using a probabilistic discounting task in which well trained male rats chose between small/certain or large/risky rewards, with the odds of obtaining the larger reward changing systematically within a session. Selective disruption of D or D modulation of separate PFC output pathways was achieved using unilateral intra-PFC infusions of DA antagonists combined with contralateral inactivation of the BLA or NAc. Disrupting D (but not D) modulation of PFC→BLA circuitry impaired adjustments in decision biases in response to changes in reward probabilities. In contrast, disrupting D modulation of PFC→NAc networks reduced risky choice, attenuating reward sensitivity and increasing sensitivity to reward omissions. These findings reveal that mesocortical DA can facilitate dissociable components of reward seeking and action selection by acting on different functional networks of PFC neurons that can be distinguished by the subcortical projection targets with which they interface. Prefrontal cortical dopamine regulates a variety of executive functions governed by the frontal lobes via actions on D and D receptors. These receptors can in some instances mediate different patterns of behavior, but the mechanisms underlying these dissociable actions are unclear. Using a selective disconnection approach, we reveal that D and D receptors can facilitate diverse aspects of decision making by acting on separate networks of prefrontal neurons that interface with distinct striatal or amygdalar targets. These findings reveal an additional level of complexity in how mesocortical DA regulates different forms of cognition via actions on different receptors, highlighting how it may act upon distinct cortical microcircuits to drive different patterns of behavior.
中脑皮质多巴胺（DA）通过作用于D1和/或D2受体来调节多种认知功能。例如，在额叶前皮质（PFC）中，这两种受体对风险/回报决策的调节方式不同，D1受体有助于灵活决策，而D2受体则促使在选择偏好中保持坚持。然而，目前尚不清楚DA如何通过作用于同一终末区域内的不同受体来介导相反的行为模式。我们探讨了DA可能作用于由D1或D2受体调节的PFC神经元的不同网络，并进而与不同的下游结构（如基底外侧杏仁核（BLA）或伏隔核（NAc））相连接的可能性。使用概率折扣任务评估决策，在该任务中，训练有素的雄性大鼠在小/确定或大/有风险的奖励之间进行选择，在一个实验过程中获得较大奖励的几率会系统地变化。通过单侧PFC内注射DA拮抗剂并结合对侧BLA或NAc失活，实现对PFC不同输出通路的D1或D2调节的选择性破坏。破坏PFC→BLA神经回路的D1（而非D2）调节会损害对奖励概率变化的决策偏差调整。相反，破坏PFC→NAc网络的D2调节会减少冒险选择，减弱奖励敏感性并增加对奖励缺失的敏感性。这些发现表明，中脑皮质DA可以通过作用于PFC神经元的不同功能网络来促进奖励寻求和行动选择的可分离成分，这些网络可以通过它们所连接的皮质下投射靶点来区分。额叶前皮质多巴胺通过作用于D1和D2受体来调节由额叶控制的多种执行功能。这些受体在某些情况下可以介导不同的行为模式，但这些可分离作用的潜在机制尚不清楚。使用选择性切断方法，我们发现D1和D2受体可以通过作用于与不同纹状体或杏仁核靶点相连接的额叶前神经元的不同网络来促进决策的不同方面。这些发现揭示了中脑皮质DA如何通过作用于不同受体来调节不同形式认知的另一个复杂层面，突出了它可能如何作用于不同的皮质微回路以驱动不同的行为模式。
