Journal article

Notch1 regulates hippocampal plasticity through interaction with the reelin pathway, glutamatergic transmission and CREB signaling

  • Brai, Emanuele Department of Medicine, Institute of Anatomy, University of Fribourg, Switzerland
  • Marathe, Swananda Department of Medicine, Institute of Anatomy, University of Fribourg, Switzerland
  • Astori, Simone Department of Fundamental Neurosciences, University of Lausanne, Switzerland
  • Fredj, Naila Ben Department of Medicine, Institute of Anatomy, University of Fribourg, Switzerland
  • Perry, Elisabeth Histology Core Laboratory, Department of Cellular Biology and Anatomy, Georgia Health Sciences University, Augusta, GA, USA
  • Lamy, Christophe M. Department of Medicine, Institute of Anatomy, University of Fribourg, Switzerland
  • Scotti, Alessandra Institute of Anatomy, Faculty of Medicine, University of Bern, Switzerland -
  • Alberi, Lavinia Department of Medicine, Institute of Anatomy, University of Fribourg, Switzerland - Unit of Pathology, Department of Medicine, University of Fribourg, Switzerland
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    26.11.2015
Published in:
  • Frontiers in Cellular Neuroscience. - 2015, p. 447
English Notch signaling plays a crucial role in adult brain function such as synaptic plasticity, memory and olfaction. Several reports suggest an involvement of this pathway in neurodegenerative dementia. Yet, to date, the mechanism underlying Notch activity in mature neurons remains unresolved. In this work, we investigate how Notch regulates synaptic potentiation and contributes to the establishment of memory in mice. We observe that Notch1 is a postsynaptic receptor with functional interactions with the Reelin receptor, apolipoprotein E receptor 2 (ApoER2) and the ionotropic receptor, N-methyl-D-aspartate receptor (NMDAR). Targeted loss of Notch1 in the hippocampal CA fields affects Reelin signaling by influencing Dab1 expression and impairs the synaptic potentiation achieved through Reelin stimulation. Further analysis indicates that loss of Notch1 affects the expression and composition of the NMDAR but not AMPAR. Glutamatergic signaling is further compromised through downregulation of CamKII and its secondary and tertiary messengers resulting in reduced cAMP response element-binding (CREB) signaling. Our results identify Notch1 as an important regulator of mechanisms involved in synaptic plasticity and memory formation. These findings emphasize the possible involvement of this signaling receptor in dementia.
Faculty
Faculté des sciences et de médecine
Department
Médecine 3ème année, Département de Médecine
Language
  • English
Classification
Biology
License
License undefined
Identifiers
Persistent URL
https://folia.unifr.ch/unifr/documents/304798
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