NAcb-DBS Enhanced Adult Hippocampal Neurogenesis in HAB Mice
To examine possible underlying mechanisms of successful NAcb-DBS, we next studied whether repeated NAcb-DBS would increase adult hippocampal neurogenesis in HAB mice, as this has been previously shown for various other antidepressant interventions, including pharmacotherapy and electroconvulsive seizures (for a review see Samuels and Hen, 2011). Indeed, in HAB mice, DCX immunohistochemistry revealed an enhanced number of immature neurons in the dentate gyrus of the HPC following repeated NAcb-DBS as compared with NAcb-sham conditions (t=2.706, P=0.015; Figures 4a and c or t=2.914, P=0.001; Figures 4e and g). In addition, BrdU was injected either before NAcb-DBS or during NAcb-DBS (see Figure 2a, Experiments 3 and 4) to reveal putatively different effects of NAcb-DBS at different developmental stages of newly born cells. It was observed that the number of BrdU-positive cells was increased following NAcb-DBS treatment as compared with NAcb-Sham condition when BrdU was injected before NAcb-DBS (t=2.361, P=0.030; Figures 4b and d), but not during NAcb-DBS (t=0.268, P=0.792; Figures 4f and h).