Milad Mohammed R, Quirk Gregory J
Department of Physiology, Ponce School of Medicine, Ponce, Puerto Rico 00732, USA.
Nature. 2002 Nov 7;420(6911):70-4. doi: 10.1038/nature01138.
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 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, 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.
如果在没有电击的情况下反复呈现先前与电击配对的音调，对该音调的条件性恐惧反应就会减弱，这个过程称为消退。自巴甫洛夫时代以来，人们一直假设消退并不会消除条件作用，而是形成一种新的记忆。腹内侧前额叶皮层由下缘皮质和前边缘皮质组成，破坏该区域会阻碍恐惧消退的回忆，这表明内侧前额叶皮层可能存储长期的消退记忆。我们在此表明，在恐惧条件作用和消退过程中记录到的下缘皮质神经元，仅在大鼠次日回忆消退时才会对音调产生放电反应。冻结反应最少的大鼠，其下缘皮质对音调的反应增加幅度最大。我们还表明，将条件性音调与对下缘皮质的短暂电刺激配对，会使尚未消退的大鼠产生低水平的冻结反应。因此，类似于消退诱导的下缘皮质音调反应的刺激能够模拟消退记忆。我们认为，消退学习的巩固增强了下缘皮质的活动，这在随后遇到恐惧刺激时会抑制恐惧。
