TY - JOUR
T1 - Activity-Induced Notch Signaling in Neurons Requires Arc/Arg3.1 and Is Essential for Synaptic Plasticity in Hippocampal Networks
AU - Alberi, Lavinia
AU - Liu, Shuxi
AU - Wang, Yue
AU - Badie, Ramy
AU - Smith-Hicks, Constance
AU - Wu, Jing
AU - Pierfelice, Tarran J.
AU - Abazyan, Bagrat
AU - Mattson, Mark P.
AU - Kuhl, Dietmar
AU - Pletnikov, Mikhail
AU - Worley, Paul F.
AU - Gaiano, Nicholas
N1 - Funding Information:
The authors thank Jason Shepherd, Richard Flannery, Marlin Dehoff, Vera Goh, and Keejung Yoon for technical and intellectual input during the course of this project. We also thank Ted Dawson and Jay Baraban for critically reading the manuscript. Funding for this work came from the Institute for Cell Engineering at Johns Hopkins University (N.G.), a NARSAD Young Investigator Award (N.G), the James S. McDonnell Foundation (N.G.), and the National Institute of Mental Health (P.F.W.).
PY - 2011/2/10
Y1 - 2011/2/10
N2 - Notch signaling in the nervous system has been most studied in the context of cell fate specification. However, numerous studies have suggested that Notch also regulates neuronal morphology, synaptic plasticity, learning, and memory. Here we show that Notch1 and its ligand Jagged1 are present at the synapse, and that Notch signaling in neurons occurs in response to synaptic activity. In addition, neuronal Notch signaling is positively regulated by Arc/Arg3.1, an activity-induced gene required for synaptic plasticity. In Arc/Arg3.1 mutant neurons, the proteolytic activation of Notch1 is disrupted both in vivo and in vitro. Conditional deletion of Notch1 in the postnatal hippocampus disrupted both long-term potentiation (LTP) and long-term depression (LTD), and led to deficits in learning and short-term memory. Thus, Notch signaling is dynamically regulated in response to neuronal activity, Arc/Arg3.1 is a context-dependent Notch regulator, and Notch1 is required for the synaptic plasticity that contributes to memory formation.
AB - Notch signaling in the nervous system has been most studied in the context of cell fate specification. However, numerous studies have suggested that Notch also regulates neuronal morphology, synaptic plasticity, learning, and memory. Here we show that Notch1 and its ligand Jagged1 are present at the synapse, and that Notch signaling in neurons occurs in response to synaptic activity. In addition, neuronal Notch signaling is positively regulated by Arc/Arg3.1, an activity-induced gene required for synaptic plasticity. In Arc/Arg3.1 mutant neurons, the proteolytic activation of Notch1 is disrupted both in vivo and in vitro. Conditional deletion of Notch1 in the postnatal hippocampus disrupted both long-term potentiation (LTP) and long-term depression (LTD), and led to deficits in learning and short-term memory. Thus, Notch signaling is dynamically regulated in response to neuronal activity, Arc/Arg3.1 is a context-dependent Notch regulator, and Notch1 is required for the synaptic plasticity that contributes to memory formation.
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U2 - 10.1016/j.neuron.2011.01.004
DO - 10.1016/j.neuron.2011.01.004
M3 - Article
C2 - 21315255
AN - SCOPUS:79551663694
SN - 0896-6273
VL - 69
SP - 437
EP - 444
JO - Neuron
JF - Neuron
IS - 3
ER -