Presenilin 1 regulates homeostatic synaptic scaling through Akt signaling

Nat Neurosci. 2011 Aug 14;14(9):1112-4. doi: 10.1038/nn.2893.

Abstract

Neurons adapt to long-lasting changes in network activity, both in vivo and in vitro, by adjusting their synaptic strengths to stabilize firing rates. We found that homeostatic scaling of excitatory synapses was impaired in hippocampal neurons derived from mice lacking presenilin 1 (Psen1(-/-) mice) or expressing a familial Alzheimer's disease-linked Psen1 mutation (Psen1(M146V)). These findings suggest that deficits in synaptic homeostasis may contribute to brain dysfunction in Alzheimer's disease.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Analysis of Variance
  • Animals
  • Animals, Newborn
  • Biophysics
  • Electric Stimulation
  • Embryo, Mammalian
  • Enzyme Inhibitors / pharmacology
  • Excitatory Postsynaptic Potentials / drug effects
  • Excitatory Postsynaptic Potentials / genetics
  • Green Fluorescent Proteins / genetics
  • Green Fluorescent Proteins / metabolism
  • Hippocampus / cytology
  • Homeostasis / drug effects
  • Homeostasis / genetics
  • Homeostasis / physiology*
  • Methionine / genetics
  • Mice
  • Mice, Inbred BALB C
  • Mice, Knockout
  • Mutation / genetics
  • Neurons / physiology*
  • Oncogene Protein v-akt / genetics
  • Oncogene Protein v-akt / metabolism*
  • Patch-Clamp Techniques / methods
  • Presenilin-1 / deficiency
  • Presenilin-1 / metabolism*
  • Signal Transduction / drug effects
  • Signal Transduction / physiology*
  • Sodium Channel Blockers / pharmacology
  • Synapses / genetics
  • Synapses / physiology*
  • Tetrodotoxin / pharmacology
  • Transfection
  • Valine / genetics

Substances

  • Enzyme Inhibitors
  • Presenilin-1
  • Sodium Channel Blockers
  • enhanced green fluorescent protein
  • Green Fluorescent Proteins
  • Tetrodotoxin
  • Methionine
  • Oncogene Protein v-akt
  • Valine