Involvement of Notch signaling in hippocampal synaptic plasticity.
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-kappa B 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.
Wang
Yue
Y
Laboratory of Neurosciences, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA.
Chan
Sic L
SL
Miele
Lucio
L
Yao
Pamela J
PJ
Mackes
Jennifer
J
Ingram
Donald K
DK
Mattson
Mark P
MP
Furukawa
Katsutoshi
K
D000818:Animals; D006624:Hippocampus / Q000502:physiology*; D007858:Learning / Q000502:physiology; D017774:Long-Term Potentiation / Q000502:physiology; D008565:Membrane Proteins / Q000235:genetics / Q000502:physiology*; D008568:Memory / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic; D009473:Neuronal Plasticity / Q000502:physiology*; D011956:Receptors, Cell Surface / Q000235:genetics / Q000502:physiology; D051880:Receptors, Notch; D013569:Synapses / Q000502:physiology*
D008565:Membrane Proteins; D011956:Receptors, Cell Surface; D051880:Receptors, Notch