Activity-Induced Notch Signaling in Neurons Requires Arc/Arg3.1 and Is Essential for Synaptic Plasticity in Hippocampal Networks

Lavinia Alberi, Shuxi Liu, Yue Wang, Ramy Badie, Constance Smith-Hicks, Jing Wu, Tarran J. Pierfelice, Bagrat Abazyan, Mark P. Mattson, Dietmar Kuhl, Mikhail Pletnikov, Paul F. Worley, Nicholas Gaiano

Research output: Research - peer-reviewArticle

Abstract

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.

LanguageEnglish (US)
Pages437-444
Number of pages8
JournalNeuron
Volume69
Issue number3
DOIs
StatePublished - Feb 10 2011

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Neuronal Plasticity
Neurons
Learning
Long-Term Potentiation
Short-Term Memory
Synapses
Nervous System
Hippocampus
Depression
Ligands
Genes
In Vitro Techniques

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Activity-Induced Notch Signaling in Neurons Requires Arc/Arg3.1 and Is Essential for Synaptic Plasticity in Hippocampal Networks. / Alberi, Lavinia; Liu, Shuxi; Wang, Yue; Badie, Ramy; Smith-Hicks, Constance; Wu, Jing; Pierfelice, Tarran J.; Abazyan, Bagrat; Mattson, Mark P.; Kuhl, Dietmar; Pletnikov, Mikhail; Worley, Paul F.; Gaiano, Nicholas.

In: Neuron, Vol. 69, No. 3, 10.02.2011, p. 437-444.

Research output: Research - peer-reviewArticle

Alberi, L, Liu, S, Wang, Y, Badie, R, Smith-Hicks, C, Wu, J, Pierfelice, TJ, Abazyan, B, Mattson, MP, Kuhl, D, Pletnikov, M, Worley, PF & Gaiano, N 2011, 'Activity-Induced Notch Signaling in Neurons Requires Arc/Arg3.1 and Is Essential for Synaptic Plasticity in Hippocampal Networks' Neuron, vol 69, no. 3, pp. 437-444. DOI: 10.1016/j.neuron.2011.01.004
Alberi, Lavinia ; Liu, Shuxi ; Wang, Yue ; Badie, Ramy ; Smith-Hicks, Constance ; Wu, Jing ; Pierfelice, Tarran J. ; Abazyan, Bagrat ; Mattson, Mark P. ; Kuhl, Dietmar ; Pletnikov, Mikhail ; Worley, Paul F. ; Gaiano, Nicholas. / Activity-Induced Notch Signaling in Neurons Requires Arc/Arg3.1 and Is Essential for Synaptic Plasticity in Hippocampal Networks. In: Neuron. 2011 ; Vol. 69, No. 3. pp. 437-444
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