Department of Psychiatry, Weill Cornell Medical College, Cornell University, New York, NY 10065, USA.
Proc Natl Acad Sci U S A. 2011 Jan 18;108(3):1182-7. doi: 10.1073/pnas.1012975108. Epub 2011 Jan 10.
Highly conserved neural circuitry between rodents and humans has allowed for in-depth characterization of behavioral and molecular processes associated with emotional learning and memory. Despite increased prevalence of affective disorders in adolescent humans, few studies have characterized how associative-emotional learning changes during the transition through adolescence or identified mechanisms underlying such changes. By examining fear conditioning in mice, as they transitioned into and out of adolescence, we found that a suppression of contextual fear occurs during adolescence. Although contextual fear memories were not expressed during early adolescence, they could be retrieved and expressed as the mice transitioned out of adolescence. This temporary suppression of contextual fear was associated with blunted synaptic activity in the basal amygdala and decreased PI3K and MAPK signaling in the hippocampus. These findings reveal a unique form of brain plasticity in fear learning during early adolescence and may prove informative for understanding endogenous mechanisms to suppress unwanted fear memories.
啮齿动物和人类之间高度保守的神经回路使得深入研究与情绪学习和记忆相关的行为和分子过程成为可能。尽管青少年人群中情感障碍的患病率有所增加，但很少有研究描述在青春期过渡期间联想性情绪学习如何变化，或确定这种变化的潜在机制。通过在小鼠过渡到青春期和青春期结束时进行恐惧条件反射研究，我们发现，在青春期期间，会出现情境恐惧的抑制。尽管在青春期早期没有表达情境恐惧记忆，但当小鼠过渡到青春期结束时，它们可以被检索并表达。这种情境恐惧的暂时抑制与基底杏仁核中突触活动的减弱以及海马中 PI3K 和 MAPK 信号的减少有关。这些发现揭示了青春期早期恐惧学习中一种独特的大脑可塑性形式，这可能有助于理解抑制不必要恐惧记忆的内源性机制。
