Repeated stress alters dendritic spine morphology in the rat medial prefrontal cortex

Authors

  • Jason J. Radley,

    Corresponding author
    1. Laboratory of Neuronal Structure and Function, Salk Institute for Biological Studies, La Jolla, California 92037
    • Laboratory of Neuronal Structure and Function, Salk Institute for Biological Studies, La Jolla, CA, 92037
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  • Anne B. Rocher,

    1. Department of Neuroscience, Mount Sinai School of Medicine, New York, New York 10029
    2. Computational Neurobiology Imaging Center, Mount Sinai School of Medicine, New York, New York 10029
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  • Alfredo Rodriguez,

    1. Department of Neuroscience, Mount Sinai School of Medicine, New York, New York 10029
    2. Computational Neurobiology Imaging Center, Mount Sinai School of Medicine, New York, New York 10029
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  • Douglas B. Ehlenberger,

    1. Department of Neuroscience, Mount Sinai School of Medicine, New York, New York 10029
    2. Computational Neurobiology Imaging Center, Mount Sinai School of Medicine, New York, New York 10029
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  • Mark Dammann,

    1. Laboratory of Neuronal Structure and Function, Salk Institute for Biological Studies, La Jolla, California 92037
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  • Bruce S. McEwen,

    1. Laboratory of Neuroendocrinology, Rockefeller University, New York, New York 10021
    2. Center for the Neurobiology of Fear and Anxiety, New York University, New York, New York 10003
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  • John H. Morrison,

    1. Computational Neurobiology Imaging Center, Mount Sinai School of Medicine, New York, New York 10029
    2. Center for the Neurobiology of Fear and Anxiety, New York University, New York, New York 10003
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  • Susan L. Wearne,

    1. Department of Neuroscience, Mount Sinai School of Medicine, New York, New York 10029
    2. Computational Neurobiology Imaging Center, Mount Sinai School of Medicine, New York, New York 10029
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  • Patrick R. Hof

    Corresponding author
    1. Department of Neuroscience, Mount Sinai School of Medicine, New York, New York 10029
    2. Computational Neurobiology Imaging Center, Mount Sinai School of Medicine, New York, New York 10029
    3. Center for the Neurobiology of Fear and Anxiety, New York University, New York, New York 10003
    • Department of Neuroscience, Mount Sinai School of Medicine, Box 1065 One Gustave L. Levy Place, New York, NY 10029
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Abstract

Anatomical alterations in the medial prefrontal cortex (mPFC) are associated with hypothalamopituitary adrenal (HPA) axis dysregulation, altered stress hormone levels, and psychiatric symptoms of stress-related mental illnesses. Functional imaging studies reveal impairment and shrinkage of the mPFC in such conditions, and these findings are paralleled by experimental studies showing dendritic retraction and spine loss following repeated stress in rodents. Here we extend this characterization to how repeated stress affects dendritic spine morphology in mPFC through the utilization of an automated approach that rapidly digitizes, reconstructs three dimensionally, and calculates geometric features of neurons. Rats were perfused after being subjected to 3 weeks of daily restraint stress (6 hours/day), and intracellular injections of Lucifer Yellow were made in layer II/III pyramidal neurons in the dorsal mPFC. To reveal spines in all angles of orientation, deconvolved high-resolution confocal laser scanning microscopy image stacks of dendritic segments were reconstructed and analyzed for spine volume, surface area, and length using a Rayburst-based automated approach (8,091 and 8,987 spines for control and stress, respectively). We found that repeated stress results in an overall decrease in mean dendritic spine volume and surface area, which was most pronounced in the distal portion of apical dendritic fields. Moreover, we observed an overall shift in the population of spines, manifested by a reduction in large spines and an increase in small spines. These results suggest a failure of spines to mature and stabilize following repeated stress and are likely to have major repercussions on function, receptor expression, and synaptic efficacy. J. Comp. Neurol. 507:1141–1150, 2008. © 2007 Wiley-Liss, Inc.

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