Secreted form of β-amyloid precursor protein shifts the frequency dependency for induction of LTD, and enhances LTP in hippocampal slices

Akihiro Ishida, Katsutoshi Furukawa, Jeffrey N. Keller, Mark P. Mattson

Research output: Contribution to journalArticle

Abstract

The secreted form of β-amyloid precursor protein (sAPPα) is released from neurons in an activity-dependent manner, and has been reported to modulate neuronal excitability in dissociated hippocampal neurons. We now report that sAPPα shifts the frequency dependence for induction of long- term depression of synaptic transmission (LTD) in hippocampal slices from adult rats. Whereas low frequency stimulation (1 Hz) of Schaffer collateral axons induced LTD of the post-synaptic response of CA1 neurons in control slices, it did not induce LTD in slices pretreated with sAPPα. On the other hand, whereas a 10 Hz stimulation normally induced neither LTD or LTP, it did induce LTD in slices pretreated with sAPPα. sAPPα potentiated LTP induced by high frequency stimulation. sAPPα induced cGMP production in hippocampal slices, and pretreatment of slices with 8-bromo-cyclic GMP mimicked the effect of sAPPα on LTD suggesting a role for cyclic GMP in modulation of LTD. The data suggest an important role for sAPPα in modulation of synaptic plasticity in the hippocampus.

Original languageEnglish (US)
Pages (from-to)2133-2137
Number of pages5
JournalNeuroReport
Volume8
Issue number9-10
StatePublished - 1997
Externally publishedYes

Keywords

  • Alzheimer's disease
  • Calcium
  • Cyclic GMP
  • Excitotoxicity
  • Learning and memory
  • Long-term potentiation
  • Phosphorylation
  • Synaptic plasticity

ASJC Scopus subject areas

  • Neuroscience(all)

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