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Deep brain stimulation (DBS) is an established therapeutic modality for the treatment of movement disorders and an emerging therapeutic approach for the treatment of disorders of mood and thought. For example, recently we have shown that DBS of the fornix may ameliorate cognitive decline associated with dementia. However, like other applications of DBS, the mechanisms mediating these clinical effects are unknown. As DBS modulates neurophysiological activity in targeted brain regions, DBS might influence cognitive function via activity-dependent regulation of hippocampal neurogenesis. Using stimulation parameters analogous to clinical high-frequency DBS, here we addressed this question in mice. We found that acute stimulation of the entorhinal cortex (EC) transiently promoted proliferation in the dentate gyrus (DG). Cells generated as a consequence of stimulation differentiated into neurons, survived …