Department of Psychology, Korea University, Seoul 136701, South Korea.
Learn Mem. 2009 Dec 24;17(1):23-34. doi: 10.1101/lm.1482910. Print 2010 Jan.
Plasticity in two input pathways into the lateral nucleus of the amygdala (LA), the medial prefrontal cortex (mPFC) and the sensory thalamus, have been suggested to underlie extinction, suppression of a previously acquired conditioned response (CR) following repeated presentations of the conditioned stimulus (CS). However, little is known about the joint dynamics of the relevant synaptic changes within the LA that accompany fear extinction. Employing a novel training procedure, in which stimulation of the medial geniculate nucleus (MGm) of the thalamus served as the CS, we tested necessary and sufficient conditions for extinction in anesthetized rats. Repeatedly applying the brain-stimulation CS was neither sufficient to produce activation of the mPFC nor behavioral extinction when the animal was under anesthesia. Only when the CS was combined with contingent stimulation of the infralimbic cortex (IL) of the mPFC was the CR markedly reduced, emulating extinction. To elucidate the nature of synaptic alterations linking the extinction procedure with CR suppression, evoked field potentials to IL and MGm stimulations were recorded in the LA. The results showed that paired stimulations of the IL and MGm significantly enhanced the neural response at the IL-LA synapses and reversed conditioning-induced synaptic potentiation at the MGm-LA synapses. Taken together, our results provide strong evidence that dual plasticity within the LA underlies suppression of conditioned fear response following extinction.
两个进入杏仁外侧核（LA）的输入通路的可塑性——内侧前额叶皮层（mPFC）和感觉丘脑——被认为是消退的基础，即在条件刺激（CS）反复呈现后，抑制先前获得的条件反应（CR）。然而，对于伴随恐惧消退的 LA 内相关突触变化的联合动力学知之甚少。采用一种新的训练程序，其中丘脑内侧膝状体核（MGm）的刺激作为 CS，我们在麻醉大鼠中测试了消退的必要和充分条件。当动物处于麻醉状态时，反复施加脑刺激 CS 既不足以产生 mPFC 的激活，也不足以产生行为消退。只有当 CS 与 mPFC 的下边缘皮层（IL）的伴随刺激结合时，CR 才会明显减少，模拟消退。为了阐明将消退程序与 CR 抑制联系起来的突触改变的性质，在 LA 中记录了对 IL 和 MGm 刺激的诱发场电位。结果表明，IL 和 MGm 的成对刺激显著增强了 IL-LA 突触处的神经反应，并逆转了 MGm-LA 突触处的条件诱导突触增强。总之，我们的结果提供了强有力的证据，表明 LA 内的双重可塑性是消退后抑制条件性恐惧反应的基础。
