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

By Conor Liston, Melinda M. Miller, D. Goldwater, J. Radley, Anne B. Rocher, Patrick R. Hof, John H. Morrison, Bruce S. McEwen. Journal of Neuroscience, 2006

944 citations recorded by the source corpus.

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.

Subfields: Behavioral Neuroscience, Biological Psychiatry, Cognitive Neuroscience

View Paper: https://www.semanticscholar.org/paper/f529c7b34cc8fa1833965db228f6c8ae7deecfb6

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Citations in the corpus

Child Development in the Context of Adversity (2012, background): “…studies demonstrate that early stress alters gene expression and induces structural changes as well as changes in connectivity in brain areas that underlie stress response physiology (Karssen et al., 2007; Liston et al., 2006; Patel, Katz, Karssen, & Lyons, 2008; Radley, Arias, & Sawchenko, 2006).”
Stress signalling pathways that impair prefrontal cortex structure and function (2009, neutral): “These dendritic changes in the rat PFC are associated with marked PFC dysfunction in attentional set shiftin”
Scholarship, Research, and Creative Work at Bryn Mawr College Scholarship, Research, and Creative Work at Bryn Mawr College (background): “…these approaches, and the last half century has witnessed a considerable shift and progress in our studies;7 yet much remains to be done for the field of ancient art, specifically sculpture, to be ranked by most archaeologists at the same "objective" level of, say, Greek epigraphy and architecture.”
Protective and damaging effects of stress mediators: central role of the brain (2006, background): “but produces dendritic growth in neurons in amygdala,(95) as well as in orbitofrontal cortex.(96) Along with many other brain regions, the amygdala and prefrontal cortex also contain adrenal steroid receptors; however, the role of adrenal steroids, excitatory amino acids, and other mediators has not”
Central effects of stress hormones in health and disease: Understanding the protective and damaging effects of stress and stress mediators. (2008, background): “Behavioral correlates of remodeling in the prefrontal cortex include impairment in attention set shifting, possibly reflecting structural remodeling in the medial prefrontal cortex (Liston et al., 2006).”
Stress- and Allostasis-Induced Brain Plasticity (2011, neutral): “result of repeated stress, whereas the orbitofrontal cortex shows greater neuronal complexity as a result of chronic stress (52).”
Brain on stress: How the social environment gets under the skin (2012, background): “In the same chronic stress models that lead to amygdala neuronal hypertrophy and shrinkage of dendrites in hippocampus, there is shrinkage of dendrites and loss of spines throughout the medial prefrontal cortex, whereas dendrites expand in the orbitofrontal cortex (66).”
Psychosocial stress reversibly disrupts prefrontal processing and attentional control (2009, background): “Previous work showed that response reversals are comparably difficult but are mediated by a network independent of the prefrontal areas that mediate attention shifts (22), in analogy to the task paradigm used in the rodent model (15).”
Brain On Stress: Vulnerability and Plasticity of the Prefrontal Cortex Over the Life Course (2013, neutral): “This shrinkage has functional consequences in that mPFCdependent cognitive tasks (i.e., set shifting) are impaired by stress, and the degree of impairment correlates with the extent of dendritic shrinkage (Liston et al., 2006).”
The stressed synapse: the impact of stress and glucocorticoids on glutamate transmission (2011, background): “The brain is also a target of stress, with animal models showing stress-induced remodelling of brain architecture, such as dendritic atrophy and loss of dendritic spines in neuronal population”
Towards a glutamate hypothesis of depression (2011, background): “…stress (21 days) induced selective impairment in attentional setshifting task (a function mediated by medial prefrontal cortex), accompanied by concomitant retraction of apical dendritic arbors in anterior cingulate cortex and extension in lateral orbitofrontal cortex (Liston et al., 2006).”
The Neurocircuitry of Fear, Stress, and Anxiety Disorders (2011, background): “Chronic stress decreases dendritic branching in the hippocampus (McEwen, 2001) and mPFC (Liston et al, 2006; Radley et al, 2004), but increases dendritic branching in the amygdala (Mitra et al, 2005; Vyas et al, 2006).”