Modality-Specific Impairment of Hippocampal CA1 Neurons of Alzheimer's Disease Model Mice

J Neurosci. 2021 Jun 16;41(24):5315-5329. doi: 10.1523/JNEUROSCI.0208-21.2021. Epub 2021 May 12.


Impairment of episodic memory, a class of memory for spatiotemporal context of an event, is an early symptom of Alzheimer's disease. Both spatial and temporal information are encoded and represented in the hippocampal neurons, but how these representations are impaired under amyloid β (Aβ) pathology remains elusive. We performed chronic imaging of the hippocampus in awake male amyloid precursor protein (App) knock-in mice behaving in a virtual reality environment to simultaneously monitor spatiotemporal representations and the progression of Aβ depositions. We found that temporal representation is preserved, whereas spatial representation is significantly impaired in the App knock-in mice. This is because of the overall reduction of active place cells, but not time cells, and compensatory hyperactivation of remaining place cells near Aβ aggregates. These results indicate the differential impact of Aβ aggregates on two major modalities of episodic memory, suggesting different mechanisms for forming and maintaining these two representations in the hippocampus.

Keywords: Alzheimer’s disease; calcium imaging; place cell; time cell; virtual reality.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Alzheimer Disease / pathology*
  • Amyloid beta-Protein Precursor / metabolism
  • Amyloid beta-Protein Precursor / toxicity
  • Animals
  • CA1 Region, Hippocampal / pathology*
  • Disease Models, Animal
  • Male
  • Memory Disorders / pathology*
  • Memory, Episodic
  • Mice
  • Neurons / pathology*


  • Amyloid beta-Protein Precursor