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

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.

Bibliografische Daten

OriginalspracheEnglisch
Aufsatznummer3
ISSN0896-6273
StatusVeröffentlicht - 2011
pubmed 21315255