Cerebral Cortex Advance Access originally published online on May 18, 2005
Cerebral Cortex 2006 16(3):313-320; doi:10.1093/cercor/bhi104
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Published by Oxford University Press 2005.
Repeated Stress Induces Dendritic Spine Loss in the Rat Medial Prefrontal Cortex
1 Department of Neuroscience, Mount Sinai School of Medicine, New York, NY 10029, USA, 2 NIMH Center for Fear and Anxiety, New York, NY, 10003, USA and 3 Laboratory of Neuroendocrinology, Rockefeller University, New York, NY 10021, USA
Address correspondence to Jason J. Radley, Laboratory of Neuronal Structure and Function, Salk Institute for Biological Studies, PO Box 85800, San Diego, CA 92310, USA. Email: radley{at}salk.edu or john.morrison{at}mssm.edu.
The prefrontal cortex (PFC) plays an important role in higher cognitive processes, and in the regulation of stress-induced hypothalamic–pituitary–adrenal (HPA) activity. Here we examined the effect of repeated restraint stress on dendritic spine number in the medial PFC. Rats were perfused after receiving 21 days of daily restraint stress, and intracellular iontophoretic injections of Lucifer Yellow were carried out in layer II/III pyramidal neurons in the anterior cingulate and prelimbic cortices. We found that stress results in a significant (16%) decrease in apical dendritic spine density in medial PFC pyramidal neurons, and confirmed a previous observation that total apical dendritic length is reduced by 20% in the same neurons. We estimate that nearly one-third of all axospinous synapses on apical dendrites of pyramidal neurons in medial PFC are lost following repeated stress. A decrease in medial PFC dendritic spines may not only be indicative of a decrease in the total population of axospinous synapses, but may impair these neurons' capacity for biochemical compartmentalization and plasticity in which dendritic spines play a major role. Dendritic atrophy and spine loss may be important cellular features of stress-related psychiatric disorders where the PFC is functionally impaired.
Key Words: axospinous synapse • cell loading • dendritic spine • post-traumatic stress disorder • prefrontal • stress
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