Stress-induced alterations in prefrontal cortical dendritic morphology predict selective impairments in perceptual attentional set-shifting.

Full Abstract

Stressful life events have been implicated clinically in the pathogenesis of mental illness, but the neural substrates that may account for this observation remain poorly understood. Attentional impairments symptomatic of these psychiatric conditions are associated with structural and functional abnormalities in a network of prefrontal cortical structures. Here, we examine whether chronic stress-induced dendritic alterations in the medial prefrontal cortex (mPFC) and orbital frontal cortex (OFC) underlie impairments in the behaviors that they subserve. After 21 d of repeated restraint stress, rats were tested on a perceptual attentional set-shifting task, which yields dissociable measures of reversal learning and attentional set-shifting, functions that are mediated by the OFC and mPFC, respectively. Intracellular iontophoretic injections of Lucifer yellow were performed in a subset of these rats to examine dendritic morphology in layer II/III pyramidal cells of the mPFC and lateral OFC. Chronic stress induced a selective impairment in attentional set-shifting and a corresponding retraction (20%) of apical dendritic arbors in the mPFC. In stressed rats, but not in controls, decreased dendritic arborization in the mPFC predicted impaired attentional set-shifting performance. In contrast, stress was not found to adversely affect reversal learning or dendritic morphology in the lateral OFC. Instead, apical dendritic arborization in the OFC was increased by 43%. This study provides the first direct evidence that dendritic remodeling in the prefrontal cortex may underlie the functional deficits in attentional control that are symptomatic of stress-related mental illnesses.

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Author information

Author/s: Liston, Conor (C); Miller, Melinda M (MM); Goldwater, Deena S (DS); Radley, Jason J (JJ); Rocher, Anne B (AB); Hof, Patrick R (PR); Morrison, John H (JH); McEwen, Bruce S (BS);

Affiliation: Laboratory of Neuroendocrinology, The Rockefeller University, New York, New York 10021, USA. cliston(-atsign-)rockefeller.edu

Grants: 5P50 MH58911 (Agency:NIMH NIH HHS) ; GM 07739 (Agency:NIGMS NIH HHS) ; MH 41256 (Agency:NIMH NIH HHS)

Journal and publication information

Publication Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't

Journal: The Journal of neuroscience : the official journal of the Society for Neuroscience (J Neurosci), published in United States. (Language: eng)

Reference: 2006-Jul; vol 26 (issue 30) : pp 7870-4

Dates: Created 2006/07/27; Completed 2006/08/14; Revised 2007/11/14;

PMID: 16870732, status: MEDLINE (last retrieval date: 12/26/2008)

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Animals
Attention Deficit Disorder with Hyperactivity - pathology; physiopathology
Dendrites - pathology
Male
Memory, Short-Term

Perceptual Disorders - pathology; physiopathology
Prefrontal Cortex - pathology; physiopathology
Rats
Rats, Sprague-Dawley
Stress, Psychological - pathology; physiopathology

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