Baker Kathryn D, Richardson Rick
School of Psychology, UNSW Australia, Sydney, New South Wales 2052, Australia
School of Psychology, UNSW Australia, Sydney, New South Wales 2052, Australia.
Learn Mem. 2015 Oct 15;22(11):537-43. doi: 10.1101/lm.039487.114. Print 2015 Nov.
Fear inhibition is markedly impaired in adolescent rodents and humans. The present experiments investigated whether this impairment is critically determined by the animal's age at the time of fear learning or their age at fear extinction. Male rats (n = 170) were tested for extinction retention after conditioning and extinction at different ages. We examined neural correlates of impaired extinction retention by detection of phosphorylated mitogen-activated protein kinase immunoreactivity (pMAPK-IR) in several brain regions. Unexpectedly, adolescent rats exhibited good extinction retention if fear was acquired before adolescence. Further, fear acquired in adolescence could be successfully extinguished in adulthood but not within adolescence. Adolescent rats did not show extinction-induced increases in pMAPK-IR in the medial prefrontal cortex or the basolateral amygdala, or a pattern of reduced caudal central amygdala pMAPK-IR, as was observed in juveniles. This dampened prefrontal and basolateral amygdala MAPK activation following extinction in adolescence occurred even when there was no impairment in extinction retention. In contrast, only adolescent animals that exhibited impaired extinction retention showed elevated pMAPK-IR in the posterior paraventricular thalamus. These data suggest that neither the animal's age at the time of fear acquisition or extinction determines whether impaired extinction retention is exhibited. Rather, it appears that forming competing fear conditioning and extinction memories in adolescence renders this a vulnerable developmental period in which fear is difficult to inhibit. Furthermore, even under conditions that promote good extinction, the neural correlates of extinction in adolescence are different than those recruited in animals of other ages.
在青春期啮齿动物和人类中,恐惧抑制能力明显受损。本实验研究了这种损伤是否主要由动物在恐惧学习时的年龄或恐惧消退时的年龄所决定。对170只雄性大鼠在不同年龄进行条件反射和消退训练后,测试其消退记忆的保持情况。我们通过检测几个脑区中磷酸化丝裂原活化蛋白激酶免疫反应性(pMAPK-IR)来检查消退记忆保持受损的神经相关性。出乎意料的是,如果在青春期前获得恐惧,青春期大鼠表现出良好的消退记忆保持。此外,青春期获得的恐惧在成年期可以成功消退,但在青春期内则不能。与幼年大鼠不同,青春期大鼠在消退训练后,内侧前额叶皮质或基底外侧杏仁核中未显示pMAPK-IR增加,也没有尾侧中央杏仁核pMAPK-IR减少的模式。即使在消退记忆保持没有受损的情况下,青春期大鼠在消退训练后前额叶和基底外侧杏仁核的MAPK激活也会减弱。相反,只有消退记忆保持受损的青春期动物在后脑室旁丘脑显示pMAPK-IR升高。这些数据表明,恐惧习得或消退时动物的年龄都不能决定是否会出现消退记忆保持受损。相反,在青春期形成相互竞争的恐惧条件反射和消退记忆似乎使这个发育阶段变得脆弱,在这个阶段恐惧难以抑制。此外,即使在促进良好消退的条件下,青春期消退的神经相关性也与其他年龄段动物的不同。