Morgan Maria A, Schulkin Jay, LeDoux Joseph E
Department of Psychology, New York University, New York, NY, USA.
Behav Brain Res. 2003 Nov 30;146(1-2):121-30. doi: 10.1016/j.bbr.2003.09.021.
Several years ago, we found that lesions of ventral medial prefrontal cortex (mPFCv) disrupted performance during the extinction component of a classical fear conditioning task without affecting acquisition performance. We called this emotional perseveration, hypothesizing that mPFCv may normally act to inhibit fear responses to a conditioned stimulus (CS) when the CS no longer signals danger. Subsequent studies have supported this hypothesis, showing that mPFCv is crucial for the memory of prior extinction training. The present study examined the effects of mPFCv lesions made after training. Such lesions resulted in reduced freezing to contextual stimuli and normal responding to the CS presented alone during a retention test. Rats were then subjected to extinction trials (CS without US) over multiple days. In contrast to pre-training lesions, post-training lesions had little effect on extinction rate. All rats were given additional training. Lesioned rats expressed greater fear reactions than controls, indicating that prior extinction was less effective in them. Lesioned rats also showed resistance to extinction during reextinction trials, confirming our earlier finding that lesions made before training weaken the effectiveness of extinction trials. These results suggest three conclusions. First, an intact mPFCv during acquisition may protect the animal from prolonged responding during extinction trials following brain insult. Second, changes in mPFCv may predispose subjects toward enhanced fear reactions that are difficult to extinguish when reexposed to fearful stimuli, due to a diminished capacity to benefit from the fear-reducing impact of prior extinction experience. Third, contextual cues processed by mPFCv may influence extinction performance.
几年前，我们发现腹内侧前额叶皮层（mPFCv）受损会破坏经典恐惧条件反射任务消退阶段的表现，但不影响习得阶段的表现。我们将此称为情绪持续性，推测mPFCv通常在条件刺激（CS）不再预示危险时，发挥抑制对该条件刺激的恐惧反应的作用。后续研究支持了这一假设，表明mPFCv对先前消退训练的记忆至关重要。本研究考察了训练后进行mPFCv损伤的影响。这种损伤导致在记忆测试期间对情境刺激的僵立反应减少，而对单独呈现的条件刺激的反应正常。然后让大鼠进行多天的消退试验（CS出现但无US）。与训练前损伤不同，训练后损伤对消退率影响很小。所有大鼠都接受了额外训练。损伤大鼠比对照组表现出更强烈的恐惧反应，表明先前的消退训练对它们效果较差。损伤大鼠在再次消退试验中也表现出对消退的抵抗，证实了我们早期的发现，即训练前的损伤会削弱消退试验的效果。这些结果得出三个结论。第一，习得过程中完整的mPFCv可能保护动物在脑损伤后的消退试验中避免长时间反应。第二，mPFCv的变化可能使个体更容易出现增强的恐惧反应，当再次暴露于恐惧刺激时难以消退，这是因为从先前消退经验的恐惧减轻影响中获益的能力下降。第三，mPFCv处理的情境线索可能影响消退表现。
