Chronic audiovisual gamma stimulation restores circuit plasticity in the aging hippocampus

Non-invasive audiovisual stimulation at 40 Hz (AuViS) promotes structural and functional plasticity in the aging hippocampus, but whether these effects persist with prolonged stimulation and advanced aging remains unknown. Chronic stimulation is critical to determine long-term cellular and molecular responses to the clinically ongoing paradigms. We investigated the effects of chronic AuViS on proliferation dynamics and adult hippocampal neurogenesis across aging. Repeated AuViS promoted the differentiation of neural stem cells towards a neuronal fate at the expense of astrogenesis, and enhanced dendritic growth and maturation of adult-born granule cells (aGCs). Responsiveness to AuViS persisted at more advanced ages, indicating that this chronic treatment can preserve neurogenic plasticity despite further aging. Unexpectedly, chronic stimulation reduced the fraction of actively cycling progenitors, raising the possibility that AuViS affects neural stem cell dynamics over time. Whether the stem cell pool changes or becomes depleted and exhausted remains to be determined in ongoing experiments. Together, these findings establish chronic AuViS as a sustained modulator of hippocampal neurogenesis and provide a framework to determine how prolonged stimulation shapes cellular plasticity during aging.