Involvement of Notch signaling in hippocampal synaptic plasticity

Yue Wang, Sic L. Chan, Lucio Miele, Pamela J. Yao, Jennifer Mackes, Donald K. Ingram, Mark P. Mattson, Katsutoshi Furukawa

Research output: Contribution to journalArticlepeer-review

189 Scopus citations


During development of the nervous system, the fate of stem cells is regulated by a cell surface receptor called Notch. Notch is also present in the adult mammalian brain; however, because Notch null mice die during embryonic development, it has proven difficult to determine the functions of Notch. Here, we used Notch antisense transgenic mice that develop and reproduce normally, but exhibit reduced levels of Notch, to demonstrate a role for Notch signaling in synaptic plasticity. Mice with reduced Notch levels exhibit impaired long-term potentiation (LTP) at hippocampal CA1 synapses. A Notch ligand enhances LTP in normal mice and corrects the defect in LTP in Notch antisense transgenic mice. Levels of basal and stimulation-induced NF-κB activity were significantly decreased in mice with reduced Notch levels. These findings suggest an important role for Notch signaling in a form of synaptic plasticity known to be associated with learning and memory processes.

Original languageEnglish (US)
Pages (from-to)9458-9462
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number25
StatePublished - Jun 22 2004


  • Alzheimer's disease
  • Learning and memory
  • Long-term depression
  • Long-term potentiation
  • NF-κB

ASJC Scopus subject areas

  • Genetics
  • General


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