Clusters of hyperactive neurons near amyloid plaques in a mouse model of Alzheimer's disease

Science. 2008 Sep 19;321(5896):1686-9. doi: 10.1126/science.1162844.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / pathology*
  • Alzheimer Disease / physiopathology*
  • Amyloid beta-Peptides / metabolism
  • Animals
  • Calcium / metabolism
  • Calcium Signaling
  • Cerebral Cortex / pathology
  • Cerebral Cortex / physiopathology*
  • Disease Models, Animal*
  • Maze Learning
  • Memory
  • Mice
  • Mice, Transgenic
  • Nerve Net / physiopathology
  • Neurons / physiology*
  • Peptide Fragments / metabolism
  • Plaque, Amyloid / chemistry
  • Plaque, Amyloid / pathology*
  • Synapses / physiology*

Substances

  • Amyloid beta-Peptides
  • Peptide Fragments
  • amyloid beta-protein (1-42)
  • Calcium