title: Optogenetic Restoration of Disrupted Slow Oscillations Halts Amyloid Deposition and Restores Calcium Homeostasis in an Animal Model of Alzheimer's Disease.
abstract: Slow oscillations are important for consolidation of memory during sleep, and Alzheimer's disease (AD) patients experience memory disturbances. Thus, we examined slow oscillation activity in an animal model of AD. APP mice exhibit aberrant slow oscillation activity. Aberrant inhibitory activity within the cortical circuit was responsible for slow oscillation dysfunction, since topical application of GABA restored slow oscillations in APP mice. In addition, light activation of channelrhodopsin-2 (ChR2) expressed in excitatory cortical neurons restored slow oscillations by synchronizing neuronal activity. Driving slow oscillation activity with ChR2 halted amyloid plaque deposition and prevented calcium overload associated with this pathology. Thus, targeting slow oscillatory activity in AD patients might prevent neurodegenerative phenotypes and slow disease progression.
authors.affiliation: Department of Neurology, MassGeneral Institute of Neurodegenerative Diseases, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, United States of America.
authors.forename: Ksenia V
authors.initials: KV
authors.lastname: Kastanenka
authors.affiliation: Department of Neurology, MassGeneral Institute of Neurodegenerative Diseases, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, United States of America.
authors.forename: Steven S
authors.initials: SS
authors.lastname: Hou
authors.affiliation: Department of Neurology, MassGeneral Institute of Neurodegenerative Diseases, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, United States of America.
authors.forename: Naomi
authors.initials: N
authors.lastname: Shakerdge
authors.affiliation: Department of Neurology, MassGeneral Institute of Neurodegenerative Diseases, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, United States of America.
authors.forename: Robert
authors.initials: R
authors.lastname: Logan
authors.affiliation: Department of Neurology, MassGeneral Institute of Neurodegenerative Diseases, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, United States of America.
authors.forename: Danielle
authors.initials: D
authors.lastname: Feng
authors.affiliation: Department of Neurology, MassGeneral Institute of Neurodegenerative Diseases, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, United States of America.
authors.forename: Susanne
authors.initials: S
authors.lastname: Wegmann
authors.affiliation: Department of Neurology, MassGeneral Institute of Neurodegenerative Diseases, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, United States of America.
authors.forename: Vanita
authors.initials: V
authors.lastname: Chopra
authors.affiliation: Department of Neurology, MassGeneral Institute of Neurodegenerative Diseases, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, United States of America.
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Hawkes
authors.affiliation: Department of Neurology, MassGeneral Institute of Neurodegenerative Diseases, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, United States of America.
authors.forename: Xiqun
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Neurology, MassGeneral Institute of Neurodegenerative Diseases, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, United States of America.
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Bacskai
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism*; D000682:Amyloid / Q000378:metabolism*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D004195:Disease Models, Animal; D015536:Down-Regulation; D006706:Homeostasis; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D062308:Optogenetics; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D000682:Amyloid; D005680:gamma-Aminobutyric Acid; D002118:Calcium