High frequency stimulation of the infralimbic cortex induces morphological changes in rat hippocampal neurons

Background: Although a significant subset of patients with major depressive disorder (MDD) fail to respond to medical or behavioural therapy, deep brain stimulation (DBS) applied to the subgenual cingulate cortex (SCC; sg25) has been shown to reduce depressive symptoms in a subset of patients. This area receives projections from neurons in the CA1 region and subiculum of the hippocampus (HC), a brain region implicated in the pathobiology and treatment of MDD. Objective: To assess whether high frequency stimulation (HFS) of the infralimbic cortex is associated with changes in cellular morphology in the HC. Methods: Rats were subjected to either infralimbic HFS or sham-stimulation. Measures of cellular morphology, including dendritic length and complexity, were assessed in pyramidal neurons in the CA1 region of the HC by means of the Golgi-Cox histological stain. Results: Dendrite length (p = 0.013) and number of branch points (p = 0.004) were significantly increased across the entire dendritic tree in animals subjected to HFS. Subsequent Scholl analysis revealed that for dendritic length these effects were localized to the region between 80 and 160 mu m from the soma (p < 0.001 for either 40 mu m interval) in the basal dendritic tree, while branch point number was predominantly increased between 120 and 160 mu m from the soma (p < 0.001) in the apical dendritic tree. Conclusions: High-frequency stimulation of the infralimbic cortex increases the complexity of apical dendrites and the length of basal dendritic trees of pyramidal neurons located in the CAl hippocampal subfield relative to sham-stimulated animals. (C) 2016 Elsevier Inc. All rights reserved.