title: Altered fear learning across development in both mouse and human.
abstract: 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.
authors.affiliation: Department of Psychiatry, Weill Cornell Medical College of Cornell University, New York, NY 10065, USA.
authors.forename: Siobhan S
authors.initials: SS
authors.lastname: Pattwell
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Duhoux
authors.forename: Catherine A
authors.initials: CA
authors.lastname: Hartley
authors.forename: David C
authors.initials: DC
authors.lastname: Johnson
authors.forename: Deqiang
authors.initials: D
authors.lastname: Jing
authors.forename: Mark D
authors.initials: MD
authors.lastname: Elliott
authors.forename: Erika J
authors.initials: EJ
authors.lastname: Ruberry
authors.forename: Alisa
authors.initials: A
authors.lastname: Powers
authors.forename: Natasha
authors.initials: N
authors.lastname: Mehta
authors.forename: Rui R
authors.initials: RR
authors.lastname: Yang
authors.forename: Fatima
authors.initials: F
authors.lastname: Soliman
authors.forename: Charles E
authors.initials: CE
authors.lastname: Glatt
authors.forename: B J
authors.initials: BJ
authors.lastname: Casey
authors.forename: Ipe
authors.initials: I
authors.lastname: Ninan
authors.forename: Francis S
authors.initials: FS
authors.lastname: Lee
mesh_terms: D000293:Adolescent; D000328:Adult; D000704:Analysis of Variance; D000818:Animals; D001008:Anxiety Disorders / Q000523:psychology* / Q000628:therapy*; D002648:Child; D003213:Conditioning, Psychological / Q000502:physiology*; D005108:Extinction, Psychological / Q000502:physiology*; D005239:Fear / Q000502:physiology*; D005260:Female; D005712:Galvanic Skin Response; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008857:Microscopy, Interference; D009473:Neuronal Plasticity / Q000502:physiology*; D017397:Prefrontal Cortex / Q000502:physiology; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism
chemical_list: D016760:Proto-Oncogene Proteins c-fos