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Chronic behavioral stress induces apical dendritic reorganization in pyramidal neurons of the medial prefrontal cortex

https://doi.org/10.1016/j.neuroscience.2004.01.006Get rights and content

Abstract

Both the hippocampus and the medial prefrontal cortex (mPFC) play an important role in the negative feedback regulation of hypothalamic–pituitary–adrenal (HPA) activity during physiologic and behavioral stress. Moreover, chronic behavioral stress is known to affect the morphology of CA3c pyramidal neurons in the rat, by reducing total branch number and length of apical dendrites. In the present study, we investigated the effects of behavioral stress on the mPFC, using the repeated restraint stress paradigm. Animals were perfused after 21 days of daily restraint, and intracellular iontophoretic injections of Lucifer Yellow were carried out in pyramidal neurons of layer II/III of the anterior cingulate cortex and prelimbic area. Cellular reconstructions were performed on apical and basal dendrites of pyramidal neurons in layer II/III of the anterior cingulate and prelimbic cortices. We observed a significant reduction on the total length (20%) and branch numbers (17%) of apical dendrites, and no significant reduction in basal dendrites. These cellular changes may impair the capacity of the mPFC to suppress the response of the HPA axis to stress, and offer an experimental model of stress-induced neocortical reorganization that may provide a structural basis for the cognitive impairments observed in post-traumatic stress disorder.

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Experimental procedures

All procedures were conducted in accordance with the Rockefeller University and Mount Sinai School of Medicine Institutional Animal Care and Use Committee. Male Sprague–Dawley rats (Charles River, Wilmington, MA, USA; 250–280 g) received restraint stress (n=6) for 6 h daily (10:00–16:00 h) with wire mesh restrainers and then returned to their home cages. Another group of unstressed controls (n=5) received no treatment. Restraint stress was performed daily for 21 days. To ensure that the

Results

Intracellular injections of LY into layer II/III pyramidal neurons in the ACC and PL cortices revealed the complete filling of apical and basal dendrites with dendritic spines throughout the entire extent of the dendritic tree (Fig. 1). LY injections were performed at a depth of 10–50 μm below the dorsal surface of the sections. Since brains were postfixed for only 2 h, there was minimal tissue shrinkage relative to standard histological and immunocytochemical procedures. All apical dendritic

Discussion

The main findings of the present study were that chronic behavioral stress induced significant decreases in the total length and number of branches on apical dendrites of pyramidal neurons in the ACC and PL of rats. Moreover, these overall reductions were manifested by decreases in branching pattern complexity in the proximal-to-medial portions of apical dendritic arbors. This study represents a departure from the Golgi impregnation method that has been used in many previous studies that

Acknowledgements

This work was supported by NIH grant MH58911. We thank W. G. M. Janssen for expert technical assistance.

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