title: Clusters of hyperactive neurons near amyloid plaques in a mouse model of Alzheimer's disease.
abstract: The neurodegeneration observed in Alzheimer's disease has been associated with synaptic dismantling and progressive decrease in neuronal activity. We tested this hypothesis in vivo by using two-photon Ca2+ imaging in a mouse model of Alzheimer's disease. Although a decrease in neuronal activity was seen in 29% of layer 2/3 cortical neurons, 21% of neurons displayed an unexpected increase in the frequency of spontaneous Ca2+ transients. These "hyperactive" neurons were found exclusively near the plaques of amyloid beta-depositing mice. The hyperactivity appeared to be due to a relative decrease in synaptic inhibition. Thus, we suggest that a redistribution of synaptic drive between silent and hyperactive neurons, rather than an overall decrease in synaptic activity, provides a mechanism for the disturbed cortical function in Alzheimer's disease.
authors.affiliation: Institut für Neurowissenschaften, Technische Universität München (TUM), 80802 München, Germany.
authors.forename: Marc Aurel
authors.initials: MA
authors.lastname: Busche
authors.forename: Gerhard
authors.initials: G
authors.lastname: Eichhoff
authors.forename: Helmuth
authors.initials: H
authors.lastname: Adelsberger
authors.forename: Dorothee
authors.initials: D
authors.lastname: Abramowski
authors.forename: Karl-Heinz
authors.initials: KH
authors.lastname: Wiederhold
authors.forename: Christian
authors.initials: C
authors.lastname: Haass
authors.forename: Matthias
authors.initials: M
authors.lastname: Staufenbiel
authors.forename: Arthur
authors.initials: A
authors.lastname: Konnerth
authors.forename: Olga
authors.initials: O
authors.lastname: Garaschuk
mesh_terms: D000544:Alzheimer Disease / Q000473:pathology* / Q000503:physiopathology*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling; D002540:Cerebral Cortex / Q000473:pathology / Q000503:physiopathology*; D004195:Disease Models, Animal; D018782:Maze Learning; D008568:Memory; D051379:Mice; D008822:Mice, Transgenic; D009415:Nerve Net / Q000503:physiopathology; D009474:Neurons / Q000502:physiology*; D010446:Peptide Fragments / Q000378:metabolism; D058225:Plaque, Amyloid / Q000737:chemistry / Q000473:pathology*; D013569:Synapses / Q000502:physiology*
chemical_list: D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D002118:Calcium