Multisensory gamma stimulation enhances adult neurogenesis and improvescognitive function in male mice with Down Syndrome

Abstract

Down syndrome (DS) has been linked with deficits in hippocampal dependent cognitive tasks and adult neurogenesis, yet treatment options are still very limited. We and others previously showed that a non-invasive multisensory gamma stimulation using light and sound at 40 Hz ameliorated Alzheimers disease pathology and symptoms in mouse models. In this study, we tested the effects of 40 Hz multisensory stimulation in the Ts65Dn mice, a mouse model of DS. For three weeks, mice were exposed daily to one hour of stimulation or one hour of ambient light and sound. Mice receiving the stimulation showed improved object recognition and spatial working memory. Using single nuclei RNA-seq and experimental validations in mouse hippocampal samples, we identified underlying expression changes in gene regulatory networks and demonstrated increased adult neurogenesis and reorganization of synapses as potential mechanisms for these improved cognitive phenotypes. Together, our data reveal a novel effect of multisensory gamma stimulation on adult neurogenesis and beneficial effects of 40 Hz treatment on cognitive function in DS model mice. Significance StatementWe present strong evidence, using a well-characterized mouse model, that the cognitive and neurogenesis deficits in Down syndrome can be improved through non-invasive multi-sensory gamma stimulation. Employing a systems biology approach, we provide extensive hippocampal single-cell resolution gene expression signatures and changes in gene regulatory networks in response to sensory gamma stimulation.