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      Post-retrieval extinction in adolescence prevents return of juvenile fear

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      1 , 1 ,
      Learning & Memory
      Cold Spring Harbor Laboratory Press

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          Abstract

          Traumatic experiences early in life can contribute to the development of mood and anxiety disorders that manifest during adolescence and young adulthood. In young rats exposed to acute fear or stress, alterations in neural development can lead to enduring behavioral abnormalities. Here, we used a modified extinction intervention (retrieval+extinction) during late adolescence (post-natal day 45 [p45]), in rats, to target auditory Pavlovian fear associations acquired as juveniles (p17 and p25). The effects of adolescent intervention were examined by assessing freezing as adults during both fear reacquisition and social transmission of fear from a cagemate. Rats underwent testing or training at three time points across development: juvenile (p17 or p25), adolescent (p45), and adult (p100). Retrieval+extinction during late adolescence prevented social reinstatement and recovery over time of fears initially acquired as juveniles (p17 and p25, respectively). Adolescence was the only time point tested here where retrieval+extinction prevented fear recall of associations acquired 20+ days earlier.

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          Most cited references76

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          Effects of stress throughout the lifespan on the brain, behaviour and cognition.

          Chronic exposure to stress hormones, whether it occurs during the prenatal period, infancy, childhood, adolescence, adulthood or aging, has an impact on brain structures involved in cognition and mental health. However, the specific effects on the brain, behaviour and cognition emerge as a function of the timing and the duration of the exposure, and some also depend on the interaction between gene effects and previous exposure to environmental adversity. Advances in animal and human studies have made it possible to synthesize these findings, and in this Review a model is developed to explain why different disorders emerge in individuals exposed to stress at different times in their lives.
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            The adolescent brain and age-related behavioral manifestations.

            L Spear (2000)
            To successfully negotiate the developmental transition between youth and adulthood, adolescents must maneuver this often stressful period while acquiring skills necessary for independence. Certain behavioral features, including age-related increases in social behavior and risk-taking/novelty-seeking, are common among adolescents of diverse mammalian species and may aid in this process. Reduced positive incentive values from stimuli may lead adolescents to pursue new appetitive reinforcers through drug use and other risk-taking behaviors, with their relative insensitivity to drugs supporting comparatively greater per occasion use. Pubertal increases in gonadal hormones are a hallmark of adolescence, although there is little evidence for a simple association of these hormones with behavioral change during adolescence. Prominent developmental transformations are seen in prefrontal cortex and limbic brain regions of adolescents across a variety of species, alterations that include an apparent shift in the balance between mesocortical and mesolimbic dopamine systems. Developmental changes in these stressor-sensitive regions, which are critical for attributing incentive salience to drugs and other stimuli, likely contribute to the unique characteristics of adolescence.
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              Dynamic mapping of human cortical development during childhood through early adulthood.

              We report the dynamic anatomical sequence of human cortical gray matter development between the age of 4-21 years using quantitative four-dimensional maps and time-lapse sequences. Thirteen healthy children for whom anatomic brain MRI scans were obtained every 2 years, for 8-10 years, were studied. By using models of the cortical surface and sulcal landmarks and a statistical model for gray matter density, human cortical development could be visualized across the age range in a spatiotemporally detailed time-lapse sequence. The resulting time-lapse "movies" reveal that (i) higher-order association cortices mature only after lower-order somatosensory and visual cortices, the functions of which they integrate, are developed, and (ii) phylogenetically older brain areas mature earlier than newer ones. Direct comparison with normal cortical development may help understanding of some neurodevelopmental disorders such as childhood-onset schizophrenia or autism.
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                Author and article information

                Journal
                Learn Mem
                Learn Mem
                learnmem
                Learning & Memory
                Cold Spring Harbor Laboratory Press
                1072-0502
                1549-5485
                October 2016
                : 23
                : 10
                : 567-575
                Affiliations
                [1 ]Department of Psychology, The University of Texas at Austin, Austin, Texas 78712-1043, USA
                Author notes
                [2]

                These authors contributed equally to this work.

                Corresponding author: marie.monfils@ 123456utexas.edu
                Article
                JonesLM043281
                10.1101/lm.043281.116
                5026207
                27634147
                ac82552f-6584-482c-a655-ab867b12fd8a
                © 2016 Jones and Monfils; Published by Cold Spring Harbor Laboratory Press

                This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first 12 months after the full-issue publication date (see http://learnmem.cshlp.org/site/misc/terms.xhtml). After 12 months, it is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/.

                History
                : 21 June 2016
                : 13 July 2016
                Funding
                Funded by: National Institute of Mental Health , open-funder-registry 10.13039/100000025;
                Award ID: 1R01MH091147
                Categories
                Research

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