Multi-sensory Gamma Stimulation Ameliorates Alzheimer's-Associated Pathology and Improves Cognition

Anthony J Martorell; Abigail L Paulson; Ho-Jun Suk; Fatema Abdurrob; Gabrielle T Drummond; Webster Guan; Jennie Z Young; David Nam-Woo Kim; Oleg Kritskiy; Scarlett J Barker; Vamsi Mangena; Stephanie M Prince; Emery N Brown; Kwanghun Chung; Edward S Boyden; Annabelle C Singer; Li-Huei Tsai

doi:10.1016/j.cell.2019.02.014

Multi-sensory Gamma Stimulation Ameliorates Alzheimer's-Associated Pathology and Improves Cognition

Cell. 2019 Apr 4;177(2):256-271.e22. doi: 10.1016/j.cell.2019.02.014. Epub 2019 Mar 14.

Authors

Anthony J Martorell¹, Abigail L Paulson², Ho-Jun Suk³, Fatema Abdurrob¹, Gabrielle T Drummond¹, Webster Guan⁴, Jennie Z Young¹, David Nam-Woo Kim¹, Oleg Kritskiy¹, Scarlett J Barker¹, Vamsi Mangena⁵, Stephanie M Prince², Emery N Brown⁶, Kwanghun Chung⁷, Edward S Boyden⁸, Annabelle C Singer², Li-Huei Tsai⁹

Affiliations

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 Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University School of Medicine, Atlanta, GA 30332, USA.
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 Chemical Engineering, MIT, Cambridge, MA, USA.
⁵ Harvard-MIT Health Sciences and Technology, Cambridge, MA 02139, USA.
⁶ 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; Institute for Medical Engineering and Science, Massachusetts Institute of Technology (MIT), Cambridge, MA, USA; Department of Anesthesia, Critical Care, and Pain Medicine, Massachusetts General Hospital, Boston, MA, 02114, USA; Harvard Medical School, Boston, MA 02115, USA.
⁷ 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; Department of Chemical Engineering, MIT, Cambridge, MA, USA; Institute for Medical Engineering and Science, Massachusetts Institute of Technology (MIT), Cambridge, MA, USA; Broad Institute of Harvard and MIT, Cambridge, MA 02139, USA.
⁸ 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.
⁹ 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

We previously reported that inducing gamma oscillations with a non-invasive light flicker (gamma entrainment using sensory stimulus or GENUS) impacted pathology in the visual cortex of Alzheimer's disease mouse models. Here, we designed auditory tone stimulation that drove gamma frequency neural activity in auditory cortex (AC) and hippocampal CA1. Seven days of auditory GENUS improved spatial and recognition memory and reduced amyloid in AC and hippocampus of 5XFAD mice. Changes in activation responses were evident in microglia, astrocytes, and vasculature. Auditory GENUS also reduced phosphorylated tau in the P301S tauopathy model. Furthermore, combined auditory and visual GENUS, but not either alone, produced microglial-clustering responses, and decreased amyloid in medial prefrontal cortex. Whole brain analysis using SHIELD revealed widespread reduction of amyloid plaques throughout neocortex after multi-sensory GENUS. Thus, GENUS can be achieved through multiple sensory modalities with wide-ranging effects across multiple brain areas to improve cognitive function.

Keywords: Alzheimer’s disease; acoustic stimulation; amyloid; astrocytes; cognition; gamma rhythms; memory; microglia; photic stimulation; vasculature.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Acoustic Stimulation / methods*
Alzheimer Disease / pathology
Alzheimer Disease / therapy*
Amyloid / metabolism
Amyloid beta-Peptides / metabolism
Animals
Auditory Perception / physiology
Brain / metabolism
Cognition / physiology*
Disease Models, Animal
Gamma Rhythm / physiology
Hippocampus / metabolism
Male
Mice
Mice, Inbred C57BL
Microglia / metabolism
Plaque, Amyloid / metabolism

Substances

Amyloid
Amyloid beta-Peptides

Abstract

Publication types

MeSH terms

Substances

Grants and funding