Clusters of hyperactive neurons near amyloid plaques in a mouse model of Alzheimer's disease.
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.
Busche
Marc Aurel
MA
Institut für Neurowissenschaften, Technische Universität München (TUM), 80802 München, Germany.
Eichhoff
Gerhard
G
Adelsberger
Helmuth
H
Abramowski
Dorothee
D
Wiederhold
Karl-Heinz
KH
Haass
Christian
C
Staufenbiel
Matthias
M
Konnerth
Arthur
A
Garaschuk
Olga
O
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*
D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D002118:Calcium