Updated project metadata. Patients with Alzheimer’s disease (AD) exhibit progressive memory loss, depression, and anxiety, accompanied by impaired adult hippocampal neurogenesis (AHN). Whether modulating AHN is sufficient to improve these cognitive and noncognitive symptoms in AD remains elusive. Here we report that chronic stimulation of hypothalamic supramammillary nucleus (SuM) during early AD restores AHN in an otherwise impaired neurogenic niche. Strikingly, activation of SuM-enhanced adult-born neurons (ABNs) is sufficient to restore memory and emotion deficits in 5×FAD mice. Interestingly, activation of SuM-enhanced ABNs in AD mice increases CA3 and CA1 activity. To probe ABN-activity-dependent changes, we performed quantitative phosphoproteomics and found activation of SuM-enhanced ABNs promotes activation of the canonical pathways related to synaptic plasticity and microglia phagocytosis. Functional assays further confirm increased CA1 long-term potentiation and enhanced microglia phagocytosis of plaques upon activation of SuM-enhanced ABNs. Our findings reveal a robust AHN-promoting strategy that is sufficient to restore AD-associated deficits and highlight ABN-activity-dependent mechanisms underlying functional improvement in AD.