Dendritic structural degeneration is functionally linked to cellular hyperexcitability in a mouse model of Alzheimer's disease

Neuron. 2014 Dec 3;84(5):1023-33. doi: 10.1016/j.neuron.2014.10.024. Epub 2014 Nov 13.


Dendritic structure critically determines the electrical properties of neurons and, thereby, defines the fundamental process of input-to-output conversion. The diversity of dendritic architectures enables neurons to fulfill their specialized circuit functions during cognitive processes. It is known that this dendritic integrity is impaired in patients with Alzheimer's disease and in relevant mouse models. It is unknown, however, whether this structural degeneration translates into aberrant neuronal function. Here we use in vivo whole-cell patch-clamp recordings, high-resolution STED imaging, and computational modeling of CA1 pyramidal neurons in a mouse model of Alzheimer's disease to show that structural degeneration and neuronal hyperexcitability are crucially linked. Our results demonstrate that a structure-dependent amplification of synaptic input to action potential output conversion might constitute a novel cellular pathomechanism underlying network dysfunction with potential relevance for other neurodegenerative diseases with abnormal changes of dendritic morphology.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials / drug effects
  • Action Potentials / genetics
  • Alzheimer Disease / complications*
  • Alzheimer Disease / genetics
  • Alzheimer Disease / pathology
  • Amyloid beta-Protein Precursor / genetics
  • Animals
  • Computer Simulation
  • Dendrites / pathology*
  • Disease Models, Animal
  • Electric Stimulation
  • Female
  • Hippocampus / pathology*
  • Humans
  • In Vitro Techniques
  • Lysine / analogs & derivatives
  • Lysine / metabolism
  • Male
  • Mice
  • Mice, Transgenic
  • Models, Neurological
  • Mutation / genetics
  • Nerve Degeneration / etiology*
  • Nerve Degeneration / pathology*
  • Neurons / pathology*
  • Presenilin-1 / genetics
  • Presenilin-1 / metabolism


  • Amyloid beta-Protein Precursor
  • PSEN1 protein, human
  • Presenilin-1
  • biocytin
  • Lysine