Publication Type	Academic Article
Authors	Pattwell S, Liston C, Jing D, Ninan I, Yang R, Witztum J, Murdock M, Dincheva I, Bath K, Casey B, Deisseroth K, Lee F
Journal	Nat Commun
Volume	7
Pagination	11475
Date Published	05/24/2016
ISSN	2041-1723
Keywords	Behavior, Animal, Fear, Memory, Neural Pathways, Prefrontal Cortex
Abstract	Fear can be highly adaptive in promoting survival, yet it can also be detrimental when it persists long after a threat has passed. Flexibility of the fear response may be most advantageous during adolescence when animals are prone to explore novel, potentially threatening environments. Two opposing adolescent fear-related behaviours-diminished extinction of cued fear and suppressed expression of contextual fear-may serve this purpose, but the neural basis underlying these changes is unknown. Using microprisms to image prefrontal cortical spine maturation across development, we identify dynamic BLA-hippocampal-mPFC circuit reorganization associated with these behavioural shifts. Exploiting this sensitive period of neural development, we modified existing behavioural interventions in an age-specific manner to attenuate adolescent fear memories persistently into adulthood. These findings identify novel strategies that leverage dynamic neurodevelopmental changes during adolescence with the potential to extinguish pathological fears implicated in anxiety and stress-related disorders.
DOI	10.1038/ncomms11475
PubMed ID	27215672
PubMed Central ID	PMC4890178