title: Dynamic changes in neural circuitry during adolescence are associated with persistent attenuation of fear memories.
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.
authors.affiliation: Fred Hutchinson Cancer Research Center, Department of Human Biology, 1100 Fairview Ave N, Seattle, Washington 98109, USA.
authors.forename: Siobhan S
authors.initials: SS
authors.lastname: Pattwell
authors.affiliation: Brain and Mind Research Institute, Weill Cornell Medical College, New York, New York 10065, USA.|Department of Psychiatry, Weill Cornell Medical College, New York, New York 10065, USA.|Sackler Institute for Developmental Psychobiology, Weill Cornell Medical College, New York, New York 10065, USA.
authors.forename: Conor
authors.initials: C
authors.lastname: Liston
authors.affiliation: Department of Psychiatry, Weill Cornell Medical College, New York, New York 10065, USA.
authors.forename: Deqiang
authors.initials: D
authors.lastname: Jing
authors.affiliation: Department of Psychiatry, New York University School of Medicine, New York, New York 10016, USA.
authors.forename: Ipe
authors.initials: I
authors.lastname: Ninan
authors.affiliation: Department of Psychiatry, Weill Cornell Medical College, New York, New York 10065, USA.
authors.forename: Rui R
authors.initials: RR
authors.lastname: Yang
authors.affiliation: Brain and Mind Research Institute, Weill Cornell Medical College, New York, New York 10065, USA.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Witztum
authors.affiliation: Brain and Mind Research Institute, Weill Cornell Medical College, New York, New York 10065, USA.
authors.forename: Mitchell H
authors.initials: MH
authors.lastname: Murdock
authors.affiliation: Department of Psychiatry, Weill Cornell Medical College, New York, New York 10065, USA.
authors.forename: Iva
authors.initials: I
authors.lastname: Dincheva
authors.affiliation: Department of Cognitive, Linguistic, and Psychological Sciences, Brown University, Providence, Rhode Island 02912, USA.
authors.forename: Kevin G
authors.initials: KG
authors.lastname: Bath
authors.affiliation: Sackler Institute for Developmental Psychobiology, Weill Cornell Medical College, New York, New York 10065, USA.
authors.forename: B J
authors.initials: BJ
authors.lastname: Casey
authors.affiliation: Departments of Bioengineering and Psychiatry and Behavioral Sciences, Howard Hughes Medical Institute, Stanford University, Stanford, California 94305, USA.
authors.forename: Karl
authors.initials: K
authors.lastname: Deisseroth
authors.affiliation: Department of Psychiatry, Weill Cornell Medical College, New York, New York 10065, USA.|Sackler Institute for Developmental Psychobiology, Weill Cornell Medical College, New York, New York 10065, USA.
authors.forename: Francis S
authors.initials: FS
authors.lastname: Lee
mesh_terms: D000367:Age Factors; D000818:Animals; D001522:Behavior, Animal / Q000502:physiology*; D003213:Conditioning, Psychological / Q000502:physiology; D003463:Cues; D005108:Extinction, Psychological / Q000502:physiology; D005239:Fear / Q000523:psychology*; D008297:Male; D008568:Memory / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D023421:Models, Animal; D009434:Neural Pathways / Q000502:physiology*; D017397:Prefrontal Cortex / Q000502:physiology*; D013116:Spinal Cord / Q000502:physiology