Normal aging is accompanied by broad loss of cognitive function in humans and rodents, including declines in cognitive flexibility. In extinction, a conditional stimulus (CS) that was previously paired with a footshock is presented alone. This procedure reliably reduces conditional freezing behavior in young adult rats. Here, we aimed to investigate how normal aging affects extinction learning. Using young (3 months) and aged (20 months) male and female Long Evans rats, we compared extinction (using 20 CS-alone presentations) to a no extinction control (equal exposure to the conditioning chamber without CS presentations) following delay fear conditioning. We found that young animals in the extinction group showed a decrease in freezing following extinction; aged animals did not. We next examined changes in neural activity using expression of the immediate early gene zif268. In young animals, extinction corresponded with decreased expression of zif268 in the basolateral amygdala and anterior retrosplenial cortex; this was not observed in aged animals. Further, aged animals showed increased zif268 expression in each region examined, suggesting that dysfunction in neural activity precedes cognitive deficits. These results demonstrate that aging impacts both extinction learning and neural activity.

正常衰老伴随着人类和啮齿动物认知功能的广泛丧失，包括认知灵活性的下降。在灭绝过程中，先前与足部电击配对的条件刺激（CS）会单独出现。该程序可靠地减少了年轻成年大鼠的条件冻结行为。在这里，我们的目的是研究正常衰老如何影响灭绝学习。使用年轻（3个月）和老年（20个月）的雄性和雌性 Long Evans 大鼠，我们将延迟恐惧条件反射后的消退（使用 20 次单独的 CS 呈现）与无消退对照（同等暴露于调节室但没有 CS 呈现）进行比较。我们发现，灭绝组中的幼年动物在灭绝后表现出冻结能力下降；年老的动物却没有。接下来，我们利用立即早期基因 zif268 的表达来检查神经活动的变化。在年幼的动物中，灭绝与基底外侧杏仁核和前压后皮层中 zif268 表达的减少相对应。在老年动物中没有观察到这一点。此外，老年动物在每个检查区域都显示出 zif268 表达增加，这表明神经活动功能障碍先于认知缺陷。这些结果表明，衰老会影响灭绝学习和神经活动。