Altered fear learning across development in both mouse and human

被引:305
作者
Pattwell, Siobhan S. [1 ,4 ]
Duhoux, Stephanie [4 ]
Hartley, Catherine A. [4 ]
Johnson, David C. [2 ,4 ]
Jing, Deqiang [1 ]
Elliott, Mark D. [1 ]
Ruberry, Erika J. [4 ]
Powers, Alisa [4 ]
Mehta, Natasha [4 ]
Yang, Rui R. [1 ]
Soliman, Fatima [1 ,4 ]
Glatt, Charles E. [1 ]
Casey, B. J. [1 ,2 ,4 ]
Ninan, Ipe [5 ]
Lee, Francis S. [1 ,3 ]
机构
[1] Cornell Univ, Weill Cornell Med Coll, Dept Psychiat, New York, NY 10065 USA
[2] Cornell Univ, Weill Cornell Med Coll, Dept Neurol & Neurosci, New York, NY 10065 USA
[3] Cornell Univ, Weill Cornell Med Coll, Dept Pharmacol, New York, NY 10065 USA
[4] Cornell Univ, Weill Cornell Med Coll, Sackler Inst Dev Psychobiol, New York, NY 10065 USA
[5] NYU, Sch Med, Dept Psychiat, New York, NY 10016 USA
基金
美国国家卫生研究院; 瑞士国家科学基金会;
关键词
MEDIAL PREFRONTAL CORTEX; MENTAL-DISORDERS; PRELIMBIC CORTEX; CONDITIONED FEAR; ADOLESCENT BRAIN; EXTINCTION; AMYGDALA; CONSOLIDATION; COMORBIDITY; PREVALENCE;
D O I
10.1073/pnas.1206834109
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
The only evidence-based behavioral treatment for anxiety and stress-related disorders involves desensitization techniques that rely on principles of extinction learning. However, 40% of patients do not respond to this treatment. Efforts have focused on individual differences in treatment response, but have not examined when, during development, such treatments may be most effective. We examined fear-extinction learning across development in mice and humans. Parallel behavioral studies revealed attenuated extinction learning during adolescence. Probing neural circuitry in mice revealed altered synaptic plasticity of prefrontal cortical regions implicated in suppression of fear responses across development. The results suggest a lack of synaptic plasticity in the prefrontal regions, during adolescence, is associated with blunted regulation of fear extinction. These findings provide insight into optimizing treatment outcomes for when, during development, exposure therapies may be most effective.
引用
收藏
页码:16318 / 16323
页数:6
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