Department of Neurosciences.
Department of Psychiatry, Douglas Mental Health University Institute, McGill University, Montreal H4H 1R3, Quebec, Canada.
J Neurosci. 2020 Feb 19;40(8):1732-1743. doi: 10.1523/JNEUROSCI.2196-19.2020. Epub 2020 Jan 17.
Reward-associated stimuli can both evoke conditioned responses and acquire reinforcing properties in their own right, becoming avidly pursued. Such conditioned stimuli (CS) can guide reward-seeking behavior in adaptive (e.g., locating food) and maladaptive (e.g., binge eating) ways. The basolateral amygdala (BLA) regulates conditioned responses evoked by appetitive CS, but less is known about how the BLA contributes to the instrumental pursuit of CS. Here we studied the influence of BLA neuron activity on both behavioral effects. Water-restricted male rats learned to associate a light-tone cue (CS) with water delivery into a port. During these Pavlovian conditioning sessions, we paired CS presentations with photo-stimulation of channelrhodopsin-2 (ChR2)-expressing BLA neurons. BLA photo-stimulation potentiated CS-evoked port entries during conditioning, indicating enhanced conditioned approach and appetitive conditioning. Next, new rats received Pavlovian conditioning without photo-stimulation. These rats then received instrumental conditioning sessions where they could press an inactive lever or an active lever that produced CS presentation, without water delivery. Rats pressed more on the active versus inactive lever, and pairing CS presentation with BLA-ChR2 photo-stimulation intensified responding for the CS. This suggests that BLA-ChR2 photo-stimulation enhanced CS incentive value. In a separate experiment, rats did not reliably self-administer BLA-ChR2 stimulations, suggesting that BLA neurons do not carry a primary reward signal. Last, intra-BLA infusions of d-amphetamine also intensified lever-pressing for the CS. The findings suggest that BLA-mediated activity facilitates CS control over behavior by enhancing both appetitive Pavlovian conditioning and instrumental pursuit of CS. Cues paired with rewards can guide animals to valuable resources such as food. Cues can also promote dysfunctional reward-seeking behavior, as in overeating. Reward-paired cues influence reward seeking through two major mechanisms. First, reward-paired cues evoke conditioned anticipatory behaviors to prepare for impending rewards. Second, reward-paired cues are powerful motivators and they can evoke pursuit in their own right. Here we show that increasing neural activity in the basolateral amygdala enhances both conditioned anticipatory behaviors and pursuit of reward-paired cues. The basolateral amygdala therefore facilitates cue-induced control over behavior by both increasing anticipation of impending rewards and making reward cues more attractive.
奖励相关的刺激既能引起条件反应，也能获得自身的强化属性，从而变得备受追捧。这种条件刺激（CS）可以指导奖励寻求行为，既可以是适应性的（例如，寻找食物），也可以是适应性的（例如，暴食）。外侧杏仁核（BLA）调节由食欲性 CS 引起的条件反应，但关于 BLA 如何促进 CS 的工具性追求知之甚少。在这里，我们研究了 BLA 神经元活动对这两种行为效应的影响。限制饮水的雄性大鼠学会将光音提示（CS）与水输送到端口联系起来。在这些巴甫洛夫条件反射课程中，我们将 CS 呈现与表达通道视紫红质-2（ChR2）的 BLA 神经元的光刺激配对。BLA 光刺激增强了条件反射期间 CS 引发的端口进入，表明条件反射接近和食欲条件反射增强。接下来，新的大鼠在没有光刺激的情况下接受巴甫洛夫式条件反射。然后，这些大鼠接受工具性条件反射课程，在这些课程中，他们可以按下一个不活跃的杠杆或一个产生 CS 呈现而不输送水的活跃杠杆。老鼠按压主动杠杆的次数多于不活跃杠杆，并且将 CS 呈现与 BLA-ChR2 光刺激配对会增强对 CS 的反应。这表明 BLA-ChR2 光刺激增强了 CS 的激励价值。在另一个实验中，大鼠没有可靠地自我管理 BLA-ChR2 刺激，这表明 BLA 神经元不携带主要的奖励信号。最后，内侧杏仁核内注射 d-苯丙胺也加强了对 CS 的杠杆按压。这些发现表明，通过增强食欲性巴甫洛夫条件反射和对 CS 的工具性追求，BLA 介导的活动促进了 CS 对行为的控制。与奖励相关的线索可以引导动物找到有价值的资源，如食物。线索也可以促进功能失调的奖励寻求行为，如暴食。与奖励相关的线索通过两种主要机制影响奖励寻求。首先，与奖励相关的线索会引起条件性的预期行为，为即将到来的奖励做准备。其次，与奖励相关的线索是强大的动机，它们本身就可以引起追求。在这里，我们表明，增加外侧杏仁核的神经活动既能增强条件性预期行为，又能增强对奖励相关线索的追求。外侧杏仁核因此通过增加对即将到来的奖励的预期和使奖励线索更具吸引力，促进了线索诱导的行为控制。
