TY - JOUR
T1 - Involvement of Notch signaling in hippocampal synaptic plasticity
AU - Wang, Yue
AU - Chan, Sic L.
AU - Miele, Lucio
AU - Yao, Pamela J.
AU - Mackes, Jennifer
AU - Ingram, Donald K.
AU - Mattson, Mark P.
AU - Furukawa, Katsutoshi
PY - 2004/6/22
Y1 - 2004/6/22
N2 - 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.
AB - 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.
KW - Alzheimer's disease
KW - Learning and memory
KW - Long-term depression
KW - Long-term potentiation
KW - NF-κB
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UR - http://www.scopus.com/inward/citedby.url?scp=3042634620&partnerID=8YFLogxK
U2 - 10.1073/pnas.0308126101
DO - 10.1073/pnas.0308126101
M3 - Article
C2 - 15190179
AN - SCOPUS:3042634620
VL - 101
SP - 9458
EP - 9462
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
SN - 0027-8424
IS - 25
ER -