In Vivo Two-Photon Calcium Imaging of Hippocampal Neurons in Alzheimer Mouse Models

Methods Mol Biol. 2018;1750:341-351. doi: 10.1007/978-1-4939-7704-8_23.


The use of in vivo two-photon microscopy in mouse models of Alzheimer's disease (AD) has propelled studies of disease mechanisms and treatments. For instance, this approach allowed for the first time to study in the intact brain the dynamics of individual amyloid plaques, and the effects of anti-amyloid therapies on plaque formation and growth. Moreover, by combining two-photon microscopy with fluorescent calcium indicators, an amyloid-dependent abnormal hyperactivity of cortical and hippocampal neurons was revealed as a primary neuronal impairment, which was not predicted from previous in vitro analyses. Here, a method for in vivo two-photon calcium imaging with single-cell and single-action potential accuracy in the hippocampus of Alzheimer mouse models is presented.

Keywords: Alzheimer’s disease; Amyloid-β; Calcium imaging; Hippocampus; In vivo imaging; Mouse models; Neuronal hyperactivity; Two-photon microscopy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / metabolism
  • Alzheimer Disease / pathology*
  • Animals
  • Calcium / metabolism*
  • Disease Models, Animal*
  • Hippocampus / metabolism
  • Hippocampus / pathology*
  • Mice
  • Neurons / metabolism
  • Neurons / pathology*
  • Optical Imaging / methods*
  • Photons


  • Calcium