title: The Role of BDNF in the Development of Fear Learning.
abstract: Brain-derived neurotrophic factor (BDNF) is a growth factor that is dynamically expressed in the brain across postnatal development, regulating neuronal differentiation and synaptic plasticity. The neurotrophic hypothesis of psychiatric mood disorders postulates that in the adult brain, decreased BDNF levels leads to altered neural plasticity, contributing to disease. Although BDNF has been established as a key factor regulating the critical period plasticity in the developing visual system, it has recently been shown to also play a role in fear circuitry maturation, which has implications for the emergence of fear-related mood disorders. This review provides a detailed overview of developmental changes in expression of BDNF isoforms, as well as their receptors across postnatal life. In addition, recent developmental studies utilizing a genetic BDNF single nucleotide polymorphism (Val66Met) knock-in mouse highlight the impact of BDNF on fear learning during a sensitive period spanning the transition into adolescent time frame. We hypothesize that BDNF in the developing brain regulates fear circuit plasticity during a sensitive period in early adolescence, and alterations in BDNF expression (genetic or environmental) have a persistent impact on fear behavior and fear-related disorders.
authors.affiliation: Department of Psychiatry, Weill Cornell Medical College of Cornell University, New York, New York. dinchev@nyspi.columbia.edu.
authors.forename: Iva
authors.initials: I
authors.lastname: Dincheva
authors.affiliation: Department of Psychiatry, Weill Cornell Medical College of Cornell University, New York, New York.
authors.forename: Niccola B
authors.initials: NB
authors.lastname: Lynch
authors.affiliation: Department of Psychiatry, Weill Cornell Medical College of Cornell University, New York, New York.|Department of Pharmacology, Weill Cornell Medical College of Cornell University, New York, New York.|Sackler Institute for Developmental Psychobiology, Weill Cornell Medical College of Cornell University, New York, New York.
authors.forename: Francis S
authors.initials: FS
authors.lastname: Lee
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D001008:Anxiety Disorders / Q000235:genetics / Q000503:physiopathology; D001921:Brain / Q000378:metabolism / Q000503:physiopathology*; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics*; D002648:Child; D003214:Conditioning, Classical / Q000502:physiology*; D003866:Depressive Disorder / Q000235:genetics / Q000503:physiopathology; D005239:Fear / Q000502:physiology; D006801:Humans; D007858:Learning; D051379:Mice; D009415:Nerve Net / Q000503:physiopathology; D009473:Neuronal Plasticity / Q000235:genetics / Q000502:physiology; D020641:Polymorphism, Single Nucleotide / Q000235:genetics
chemical_list: D019208:Brain-Derived Neurotrophic Factor; C579455:BDNF protein, human
keywords: BDNF prodomain; adolescence; anxiety; extinction learning; fear conditioning; polymorphism