Neurons in medial prefrontal cortex signal memory for fear extinction
Neurons in medial prefrontal cortex signal memory for fear extinction
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DOI：
10.1038/nature01138
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发表时间：
2002-11-07
期刊：
影响因子：
64.8
通讯作者：
Quirk, GJ
中科院分区：
文献类型：
--
作者：
Milad, MR;Quirk, GJ
如果在没有电击的情况下重复出现该音调，则对先前与电击配对的音调的条件性恐惧反应会减弱，这一过程称为消退。自巴甫洛夫（1）以来，人们一直假设消退不会消除条件作用，而是形成新的记忆。腹侧内侧前额叶皮层（由边缘下皮层和前边缘皮层组成）的破坏会阻碍恐惧消退的回忆 (2,3)，表明内侧前额叶皮层可能会存储长期消退记忆。在这里，我们发现，只有当老鼠在第二天回忆起灭绝事件时，在恐惧条件反射和灭绝过程中记录的边缘下神经元才会发出声音。僵住最少的老鼠表现出边缘下音调反应的最大增加。我们还表明，条件音调与边缘下皮层的短暂电刺激相结合，会在大鼠中引起尚未熄灭的低度冻结。因此，类似于消退引起的边缘下音调反应的刺激能够模拟消退记忆。我们认为，消退学习的巩固会增强边缘下的活动，从而在随后遇到恐惧刺激时抑制恐惧。
Conditioned fear responses to a tone previously paired with a shock diminish if the tone is repeatedly presented without the shock, a process known as extinction. Since Pavlov(1) it has been hypothesized that extinction does not erase conditioning, but forms a new memory. Destruction of the ventral medial prefrontal cortex, which consists of infralimbic and prelimbic cortices, blocks recall of fear extinction(2,3), indicating that medial prefrontal cortex might store long-term extinction memory. Here we show that infralimbic neurons recorded during fear conditioning and extinction fire to the tone only when rats are recalling extinction on the following day. Rats that froze the least showed the greatest increase in infralimbic tone responses. We also show that conditioned tones paired with brief electrical stimulation of infralimbic cortex elicit low freezing in rats that had not been extinguished. Thus, stimulation resembling extinction-induced infralimbic tone responses is able to simulate extinction memory. We suggest that consolidation of extinction learning potentiates infralimbic activity, which inhibits fear during subsequent encounters with fear stimuli.