title: Activity-induced Notch signaling in neurons requires Arc/Arg3.1 and is essential for synaptic plasticity in hippocampal networks.
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.
authors.affiliation: Institute for Cell Engineering, Neuroregeneration Program, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. lavinia.alberi@unifr.ch
authors.forename: Lavinia
authors.initials: L
authors.lastname: Alberi
authors.forename: Shuxi
authors.initials: S
authors.lastname: Liu
authors.forename: Yue
authors.initials: Y
authors.lastname: Wang
authors.forename: Ramy
authors.initials: R
authors.lastname: Badie
authors.forename: Constance
authors.initials: C
authors.lastname: Smith-Hicks
authors.forename: Jing
authors.initials: J
authors.lastname: Wu
authors.forename: Tarran J
authors.initials: TJ
authors.lastname: Pierfelice
authors.forename: Bagrat
authors.initials: B
authors.lastname: Abazyan
authors.forename: Mark P
authors.initials: MP
authors.lastname: Mattson
authors.forename: Dietmar
authors.initials: D
authors.lastname: Kuhl
authors.forename: Mikhail
authors.initials: M
authors.lastname: Pletnikov
authors.forename: Paul F
authors.initials: PF
authors.lastname: Worley
authors.forename: Nicholas
authors.initials: N
authors.lastname: Gaiano
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D003598:Cytoskeletal Proteins / Q000502:physiology*; D006624:Hippocampus / Q000502:physiology*; D018782:Maze Learning / Q000502:physiology; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008818:Mice, Neurologic Mutants; D009415:Nerve Net / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000502:physiology*; D009473:Neuronal Plasticity / Q000502:physiology*; D009474:Neurons / Q000502:physiology; D051881:Receptor, Notch1 / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D013569:Synapses / Q000502:physiology
chemical_list: D003598:Cytoskeletal Proteins; D009419:Nerve Tissue Proteins; C497762:Notch1 protein, mouse; D051881:Receptor, Notch1; C092069:activity regulated cytoskeletal-associated protein