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The Journal of Neuroscience, July 26, 2006, 26(30):7870-7874; doi:10.1523/JNEUROSCI.1184-06.2006

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Brief Communications
Stress-Induced Alterations in Prefrontal Cortical Dendritic Morphology Predict Selective Impairments in Perceptual Attentional Set-Shifting

Conor Liston,¹ Melinda M. Miller,¹ Deena S. Goldwater,² Jason J. Radley,³ Anne B. Rocher,² Patrick R. Hof,² John H. Morrison,² and Bruce S. McEwen¹

¹Laboratory of Neuroendocrinology, The Rockefeller University, New York, New York 10021, ²Department of Neuroscience, Mount Sinai School of Medicine, New York, New York 10029, ³Laboratory of Neuronal Structure and Function, The Salk Institute for Biological Studies, La Jolla, California 92186

Correspondence should be addressed to Conor Liston, Laboratory of Neuroendocrinology, The Rockefeller University, 1230 York Avenue, Box 165, New York, NY 10021. cliston{at}rockefeller.edu

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.

Key words: stress; attention; anterior cingulate cortex; lateral orbitofrontal cortex; cell loading; dendrite

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Received March 19, 2006; revised May 25, 2006; accepted May 27, 2006.

Correspondence should be addressed to Conor Liston, Laboratory of Neuroendocrinology, The Rockefeller University, 1230 York Avenue, Box 165, New York, NY 10021. cliston{at}rockefeller.edu

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