School of Psychology, The University of New South Wales, Sydney, NSW 2052, Australia.
Learn Mem. 2013 Mar 19;20(4):220-8. doi: 10.1101/lm.029744.112.
We used Pavlovian counterconditioning in rats to identify the neural mechanisms for appetitive-aversive motivational interactions. In Stage I, rats were trained on conditioned stimulus (CS)-food (unconditioned stimulus [US]) pairings. In Stage II, this appetitive CS was transformed into a fear CS via pairings with footshock. The development of fear responses was retarded in rats that had received Stage I appetitive training. This counterconditioning was associated with increased levels of phosphorylated mitogen activated protein kinase immunoreactivity (pMAPK-IR) in several brain regions, including midline thalamus, rostral agranular insular cortex (RAIC), lateral amygdala, and nucleus accumbens core and shell, but decreased expression in the ventrolateral quadrant of the midbrain periaqueductal gray. These brain regions showing differential pMAPK-IR have previously been identified as part of the fear prediction error circuit. We then examined the causal role of RAIC MAPK in fear learning and showed that Stage II fear learning was prevented by RAIC infusions of the MEK inhibitor PD098059 (0.5 µg/hemisphere). Taken together, these results show that there are opponent interactions between the appetitive and aversive motivational systems during fear learning and that the transformation of a reward CS into a fear CS is linked to heightened activity in the fear prediction error circuit.
我们使用巴甫洛夫条件反射来鉴定大鼠中与食欲和厌恶动机相互作用有关的神经机制。在第一阶段，大鼠接受条件刺激（CS）-食物（非条件刺激[US]）配对训练。在第二阶段，通过与足底电击配对，将这种食欲 CS 转化为恐惧 CS。在接受第一阶段食欲训练的大鼠中，恐惧反应的发展受到抑制。这种条件反射与几种脑区中磷酸化丝裂原激活蛋白激酶免疫反应性（pMAPK-IR）水平的升高有关，包括中线丘脑、前岛叶皮质（RAIC）、外侧杏仁核和伏隔核核心和壳，但在中脑导水管周围灰质腹外侧象限的表达减少。这些表现出差异 pMAPK-IR 的脑区先前已被鉴定为恐惧预测误差回路的一部分。然后，我们检查了 RAIC MAPK 在恐惧学习中的因果作用，并表明 RAIC 中 MEK 抑制剂 PD098059（0.5 µg/半脑）的输注可阻止第二阶段的恐惧学习。总之，这些结果表明，在恐惧学习过程中，食欲和厌恶动机系统之间存在对立相互作用，并且将奖励 CS 转化为恐惧 CS 与恐惧预测误差回路的活性增强有关。
