Neurogenic Hippocampal Targets of Deep Brain Stimulation

Deep brain stimulation (DBS) is being used to treat movement, neurological, and psychiatric disorders; recently it has been successfully applied to patients with treatment-resistant depression or in minimally conscious state. In addition to its clinical importance, DBS presents a powerful approach to target specific neural circuits and determine the functional relationship between the components of these circuits. We examined the effect of high-frequency stimulation of a crucial component of the limbic circuitry, the anterior thalamic nuclei (ATN), on the generation of new neurons in the dentate gyrus (DG) of the hippocampus, another component of the same circuitry. Adult hippocampal neurogenesis emerges as a strong correlate of antidepressant treatments; however, in most cases, the progenitor cell population targeted by a specific treatment is not known. Using reporter mouse lines designed to quantify changes in selected classes of neural progenitors, we found that high-frequency stimulation of the ATN increases symmetric divisions of a defined class of neural progenitors in the DG; this effect is later manifested as an increased number of new neurons. The affected class of neural progenitors is also affected by the antidepressant fluoxetine (Prozac) and physical exercise (running). This indicates that neurogenic stimuli of different natures can converge on the same neurogenic target in the DG. Our results also suggest that hippocampal neurogenesis may be used as a sensitive indicator of the limbic circuitry activation induced by DBS. J. Comp. Neurol. 519:6-20, 2011. (C) 2010 Wiley-Liss, Inc.