Chinnakkaruppan Adaikkan1, Steven J Middleton2, Asaf Marco1, Ping-Chieh Pao1, Hansruedi Mathys1, David Nam-Woo Kim1, Fan Gao1, Jennie Z Young1, Ho-Jun Suk3, Edward S Boyden4, Thomas J McHugh2, Li-Huei Tsai5. 1. Picower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. 2. Laboratory for Circuit and Behavioral Physiology, RIKEN Center for Brain Science, Wako-shi, Saitama 351-0198, Japan. 3. McGovern Institute for Brain Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; MIT Media Lab, Departments of Biological Engineering and Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Harvard-MIT Health Sciences and Technology, Cambridge, MA 02139, USA. 4. Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; McGovern Institute for Brain Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; MIT Media Lab, Departments of Biological Engineering and Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. 5. Picower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Broad Institute of Harvard and MIT, Cambridge, MA 02139, USA. Electronic address: lhtsai@mit.edu.
Abstract
Neuronal and synaptic loss is characteristic in many neurodegenerative diseases, such as frontotemporal dementia and Alzheimer's disease. Recently, we showed that inducing gamma oscillations with visual stimulation (gamma entrainment using sensory stimuli, or GENUS) reduced amyloid plaques and phosphorylated tau in multiple mouse models. Whether GENUS can affect neurodegeneration or cognitive performance remains unknown. Here, we demonstrate that GENUS can entrain gamma oscillations in the visual cortex, hippocampus, and prefrontal cortex in Tau P301S and CK-p25 mouse models of neurodegeneration. Tau P301S and CK-p25 mice subjected to chronic, daily GENUS from the early stages of neurodegeneration showed a preservation of neuronal and synaptic density across multiple brain areas and modified cognitive performance. Our transcriptomic and phosphoproteomic data suggest that chronic GENUS shifts neurons to a less degenerative state, improving synaptic function, enhancing neuroprotective factors, and reducing DNA damage in neurons while also reducing inflammatory response in microglia.
Neuronal and synpan class="Gene">aptic loss is characteristic in many neurodegenerative diseases, such as frontotemporal dementia and Alzheimer's disease. Recently, we showed that inducing gamma oscillations with visual stimulation (gamma entrainment using sensory stimuli, or GENUS) reduced amyloid plaques and phosphorylated tau in multiple mouse models. Whether GENUS can affect neurodegeneration or cognitive performance remains unknown. Here, we demonstrate that GENUS can entrain gamma oscillations in the visual cortex, hippocampus, and prefrontal cortex in Tau P301S and CK-p25mouse models ofneurodegeneration. Tau P301S and CK-p25mice subjected to chronic, daily GENUS from the early stages ofneurodegeneration showed a preservation of neuronal and synaptic density across multiple brain areas and modified cognitive performance. Our transcriptomic and phosphoproteomic data suggest that chronic GENUS shifts neurons to a less degenerative state, improving synaptic function, enhancing neuroprotective factors, and reducing DNA damage in neurons while also reducing inflammatory response in microglia.
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