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Dynamic changes in neural circuitry during adolescence are associated with persistent attenuation of fear memories.

TitleDynamic changes in neural circuitry during adolescence are associated with persistent attenuation of fear memories.
Publication TypeJournal Article
Year of Publication2016
AuthorsPattwell SS, Liston C, Jing D, Ninan I, Yang RR, Witztum J, Murdock MH, Dincheva I, Bath KG, Casey BJ, Deisseroth K, Lee FS
JournalNat Commun
Volume7
Pagination11475
Date Published2016 05 24
ISSN2041-1723
KeywordsAge Factors, Animals, Behavior, Animal, Conditioning (Psychology), Cues, Extinction, Psychological, Fear, Male, Memory, Mice, Mice, Inbred C57BL, Models, Animal, Neural Pathways, Prefrontal Cortex, Spinal Cord
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.

DOI10.1038/ncomms11475
Alternate JournalNat Commun
PubMed ID27215672
PubMed Central IDPMC4890178
Grant ListR01 HD076914 / HD / NICHD NIH HHS / United States
P50 MH079513 / MH / NIMH NIH HHS / United States
R01 NS052819 / NS / NINDS NIH HHS / United States
R00 MH097822 / MH / NIMH NIH HHS / United States
T32 HD055177 / HD / NICHD NIH HHS / United States
K99 MH097822 / MH / NIMH NIH HHS / United States