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

Siobhan S. Pattwell, Conor Liston, Deqiang Jing, Ipe Ninan, Rui R. Yang, Jonathan Witztum, Mitchell H. Murdock, Iva Dincheva, Kevin G. Bath, B. J. Casey, Karl Deisseroth and Francis S. Lee ()
Additional contact information
Siobhan S. Pattwell: Fred Hutchinson Cancer Research Center
Conor Liston: Brain and Mind Research Institute, Weill Cornell Medical College
Deqiang Jing: Weill Cornell Medical College
Ipe Ninan: New York University School of Medicine
Rui R. Yang: Weill Cornell Medical College
Jonathan Witztum: Brain and Mind Research Institute, Weill Cornell Medical College
Mitchell H. Murdock: Brain and Mind Research Institute, Weill Cornell Medical College
Iva Dincheva: Weill Cornell Medical College
Kevin G. Bath: Linguistic, and Psychological Sciences, Brown University
B. J. Casey: Sackler Institute for Developmental Psychobiology, Weill Cornell Medical College
Karl Deisseroth: Howard Hughes Medical Institute, Stanford University
Francis S. Lee: Weill Cornell Medical College

Nature Communications, 2016, vol. 7, issue 1, 1-9

Abstract: 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.

Date: 2016
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DOI: 10.1038/ncomms11475

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