Neural correlates of appetitive-aversive interactions in Pavlovian fear conditioning
Neural correlates of appetitive-aversive interactions in Pavlovian fear conditioning
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DOI：
10.1101/lm.029744.112
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发表时间：
2013-04-01
影响因子：
2
通讯作者：
McNally, Gavan P.
中科院分区：
文献类型：
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作者：
Nasser, Helen M.;McNally, Gavan P.
我们利用大鼠的巴甫洛夫反条件反射来确定食欲-厌恶动机相互作用的神经机制。在第一阶段，大鼠进行条件刺激(CS)-食物（非条件刺激[US]）配对训练。在第二阶段，通过与脚震的配对，这种食欲性神经刺激转变为恐惧性神经刺激。在接受第一阶段食欲训练的大鼠中，恐惧反应的发展被延缓。这种对抗条件与几个脑区磷酸化丝裂原激活蛋白激酶免疫反应性（pMAPK-IR）水平升高有关，包括丘脑中线、吻侧颗粒岛皮层（RAIC）、外侧杏仁核和伏隔核核和壳，但中脑导水管周围灰质腹外侧象限的表达降低。这些显示不同pMAPK-IR的大脑区域之前被确定为恐惧预测错误电路的一部分。然后，我们研究了RAIC MAPK在恐惧学习中的因果作用，并发现在RAIC中注入MEK抑制剂PD098059 （0.5 μ g/半球）可以阻止II期恐惧学习。综上所述，这些结果表明，在恐惧学习过程中，食欲动机系统和厌恶动机系统之间存在对立的相互作用，并且奖励CS向恐惧CS的转变与恐惧预测错误回路的活动增强有关。
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 mu g/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.