Maternal care during infancy regulates the development of neural systems mediating the expression of fearfulness in the rat
Maternal care during infancy regulates the development of neural systems mediating the expression of fearfulness in the rat
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DOI：
10.1073/pnas.95.9.5335
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发表时间：
1998-04-28
影响因子：
11.1
通讯作者：
Meaney, MJ
中科院分区：
文献类型：
--
作者：
Caldji, C;Tannenbaum, B;Meaney, MJ
幼鼠的母亲在舔舐/梳理以及弓背哺育幼崽（LG - ABN）的频率上存在个体差异，这导致了幼崽对压力的行为反应的个体差异的发展。成年后，与低LG - ABN母亲的后代相比，高LG - ABN母亲的后代在面对新事物时表现出的行为恐惧显著减少。此外，高LG - ABN母亲的成年后代表现出：（i）杏仁核的中央核、外侧核和基底外侧核以及蓝斑中中枢苯二氮卓受体密度显著增加；（ii）蓝斑中α(2)肾上腺素能受体密度增加；（iii）蓝斑中促肾上腺皮质激素释放激素（CRH）受体密度降低。恐惧和焦虑的表达受神经回路调节，该回路包括从蓝斑到前脑结构的去甲肾上腺素能上行投射的激活。考虑到杏仁核的重要性，特别是杏仁核到蓝斑的CRH投射的致焦虑影响，以及苯二氮卓类药物的抗焦虑作用对压力行为反应表达的影响，这些发现表明，幼年期的母性关怀通过改变介导恐惧的神经系统的发育，对后代的压力行为反应进行“编程”。
The mothers of infant rats show individual differences in the frequency of licking/grooming and arched-back nursing (LG-ABN) of pups that contribute to the development of individual differences in behavioral responses to stress. As adults, the offspring of mothers that exhibited high levels of LG-ABN showed substantially reduced behavioral fearfulness in response to novelty compared with the offspring of low LG-ABN mothers. In addition, the adult offspring of the high LG-ABN mothers showed significantly (i) increased central benzodiazepine receptor density in the central, lateral, and basolateral nuclei of the amygdala as well as in the locus ceruleus, (ii) increased alpha(2) adrenoreceptor density in the locus ceruleus, and (iii) decreased corticotropin-releasing hormone (CRH) receptor density in the locus ceruleus, The expression of fear and anxiety is regulated by a neural circuitry that includes the activation of ascending noradrenergic projections from the locus ceruleus to the forebrain structures. Considering the importance of the amygdala, notably the anxiogenic influence of CRH projections from the amygdala to the locus ceruleus, as well as the anxiolytic actions of benzodiazepines, for the expression of behavioral responses to stress, these findings suggest that maternal care during infancy serves to "program" behavioral responses to stress in the offspring by altering the development of the neural systems that mediate fearfulness.