Altered fear learning across development in both mouse and human

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 109; no. 40; pp. 16318 - 16323
• Main Authors: Pattwell, Siobhan S, Duhoux, Stéphanie, Hartley, Catherine A, Johnson, David C, Jing, Deqiang, Elliott, Mark D, Ruberry, Erika J, Powers, Alisa, Mehta, Natasha, Yang, Rui R, Soliman, Fatima, Glatt, Charles E, Casey, B. J, Ninan, Ipe, Lee, Francis S
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 02.10.2012; National Acad Sciences
• Subjects: Adolescence; Adolescent; Adolescents; Adult; Adults; Analysis of Variance; Animals; anxiety; Anxiety Disorders - psychology; Anxiety Disorders - therapy; Behavioral neuroscience; Biological Sciences; Child; Conditioning (Psychology) - physiology; Extinction, Psychological - physiology; Fear; Fear - physiology; fearfulness; Female; Galvanic Skin Response; Humans; Immunohistochemistry; Learning; Male; Memory; Mice; Microscopy, Interference; Neuronal Plasticity - physiology; Neurons; patients; Prefrontal Cortex - physiology; Proto-Oncogene Proteins c-fos - metabolism; Social Sciences; Synaptic transmission
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.1206834109

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.