Audiovisual gamma stimulation restores hippocampal neurogenesis and neural circuit plasticity in aging mice

Aging is the primary risk factor for cognitive decline and neurodegenerative disorders, characterized by impaired circuit plasticity and disrupted gamma oscillations. Non-invasive 40 Hz audiovisual stimulation (AuViS) has emerged as a promising strategy to restore cognition in models of Alzheimer's disease and stroke. Yet, the mechanisms underlying these effects remain unclear. We found that AuViS increased gamma oscillations in the dentate gyrus of middle-aged mice. Control animals displayed scarce neurogenesis, and newborn neurons exhibited limited growth and remained functionally immature. Notably, AuViS triggered the proliferation of neural progenitor cells and shifted the balance from astrocytic towards neuronal differentiation. It also promoted neuronal maturation, leading to the development of complex dendritic trees and axons with large mossy terminals bearing filopodial extensions. These structural modifications were accompanied by increased spiking capacity and spontaneous synaptic activity, indicative of effective circuit integration. These effects were dependent on TrkB signaling, implicating neurotrophin pathways. Our findings demonstrate that AuViS reestablishes neurogenesis and promotes network remodeling in the healthy aging brain, which might aid to ameliorate neurological conditions.