title: Age-dependent sensitivity to glucocorticoids in the developing mouse basolateral nucleus of the amygdala.
abstract: Experiences of severe trauma during childhood are thought to be risk factors for developing mental disorders, such as anxiety and mood disorders, later in life. Correspondingly, exposure of rodents to early-life stress has been shown to affect neuronal circuitry and emotional behavior in adulthood, indicating a significant impact of stress on brain development. One current hypothesis proposes that the developing central nervous system is more sensitive to environmental influences, such as stress, than the adult. To test this hypothesis, we compared long-lasting effects of systemic corticosterone (CORT) administrations in two distinct early developmental periods. Mice exposed to early-neonatal CORT treatment on postnatal days (PD) 2-4 exhibited strongly enhanced excitability of neurons of the basolateral nucleus of the amygdala (BLA) in early adolescence and displayed impaired extinction of contextually conditioned fear memory, a type of behavior in which the BLA plays an important role. Furthermore, gene-expression of NMDA receptor subunits as well as calcium-activated K(+)-channels was reduced in the amygdala. In contrast, exposure to the same CORT concentrations in a late-neonatal period (PD17-19) did not significantly affect BLA electrophysiology or extinction learning in adolescence. These results suggest age-dependent consequences of neonatal CORT exposure in amygdala neurons and provide evidence for a detrimental influence of early-neonatal stress on adolescent fear-memory processing.
authors.affiliation: Department of Degenerative Neurological Diseases, National Institute of Neuroscience, National Center of Neurology and Psychiatry, 4-1-1 Ogawahigashi, Kodaira, Tokyo 187-8502, Japan; Department of Neurophysiology and Neuropharmacology, Center for Physiology and Pharmacology, Medical University of Vienna, 1090 Vienna, Austria; CREST, Japan Science and Technology Agency, 4-1-8 Hon-machi, Kawaguchi, Saitama 322-0012, Japan.
authors.forename: Peter
authors.initials: P
authors.lastname: Koppensteiner
authors.affiliation: Department of Degenerative Neurological Diseases, National Institute of Neuroscience, National Center of Neurology and Psychiatry, 4-1-1 Ogawahigashi, Kodaira, Tokyo 187-8502, Japan.
authors.forename: Shu
authors.initials: S
authors.lastname: Aizawa
authors.affiliation: Department of Degenerative Neurological Diseases, National Institute of Neuroscience, National Center of Neurology and Psychiatry, 4-1-1 Ogawahigashi, Kodaira, Tokyo 187-8502, Japan; CREST, Japan Science and Technology Agency, 4-1-8 Hon-machi, Kawaguchi, Saitama 322-0012, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Yamada
authors.affiliation: Department of Degenerative Neurological Diseases, National Institute of Neuroscience, National Center of Neurology and Psychiatry, 4-1-1 Ogawahigashi, Kodaira, Tokyo 187-8502, Japan.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Kabuta
authors.affiliation: Department of Neurophysiology and Neuropharmacology, Center for Physiology and Pharmacology, Medical University of Vienna, 1090 Vienna, Austria.
authors.forename: Stefan
authors.initials: S
authors.lastname: Boehm
authors.affiliation: Department of Degenerative Neurological Diseases, National Institute of Neuroscience, National Center of Neurology and Psychiatry, 4-1-1 Ogawahigashi, Kodaira, Tokyo 187-8502, Japan; CREST, Japan Science and Technology Agency, 4-1-8 Hon-machi, Kawaguchi, Saitama 322-0012, Japan.
authors.forename: Keiji
authors.initials: K
authors.lastname: Wada
authors.affiliation: Department of Degenerative Neurological Diseases, National Institute of Neuroscience, National Center of Neurology and Psychiatry, 4-1-1 Ogawahigashi, Kodaira, Tokyo 187-8502, Japan; CREST, Japan Science and Technology Agency, 4-1-8 Hon-machi, Kawaguchi, Saitama 322-0012, Japan. Electronic address: elec1@ncnp.go.jp.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Sekiguchi
mesh_terms: D000375:Aging / Q000502:physiology*; D000679:Amygdala / Q000166:cytology / Q000187:drug effects* / Q000254:growth & development*; D000818:Animals; D000831:Animals, Newborn / Q000523:psychology; D005239:Fear / Q000523:psychology; D005260:Female; D005938:Glucocorticoids / Q000494:pharmacology*; D066298:In Vitro Techniques; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D018408:Patch-Clamp Techniques; D024681:Potassium Channels, Calcium-Activated / Q000378:metabolism; D011247:Pregnancy; D016194:Receptors, N-Methyl-D-Aspartate / Q000096:biosynthesis
chemical_list: D005938:Glucocorticoids; D024681:Potassium Channels, Calcium-Activated; D016194:Receptors, N-Methyl-D-Aspartate
keywords: Basolateral amygdala; Corticosterone; Fear extinction; Neuronal excitability; Postnatal development; Stress