title: Time-dependent changes in the mouse hippocampal synaptic membrane proteome after contextual fear conditioning.
abstract: A change in efficacy of hippocampal synapses is critical for memory formation. So far, the molecular analysis of synapses during learning has focused on small groups of proteins, whereas the dynamic global changes at these synapses have remained unknown. Here, we analyzed the temporal changes of the mouse hippocampal synaptic membrane proteome 1 and 4 h after contextual fear learning, comparing two groups; (1) a fear memory forming "delayed-shock" group and (2) a fear memory-deficient "immediate-shock" group. No changes in protein expression were observed 1 h after conditioning between the two experimental groups. However, 423 proteins were significantly regulated 4 h later of which 164 proteins showed a temporal regulation after a delayed shock and 273 proteins after the stress of an immediate shock. From the proteins that were differentially regulated between the delayed- and the immediate-shock groups at 4 h, 48 proteins, most prominently representing endocytosis, (amphiphysin, dynamin, and synaptojanin1), glutamate signaling (glutamate [NMDA] receptor subunit epsilon-1, disks large homolog 3), and neurotransmitter metabolism (excitatory amino acid transporter 1, excitatory amino acid transporter 2, sodium- and chloride-dependent GABA transporter 3) were regulated in both protocols, but in opposite directions, pointing toward an interaction of learning and stress. Taken together, this data set yields novel insight into diverse and dynamic changes that take place at hippocampal synapses over the time course of contextual fear-memory learning.
authors.affiliation: Department of Molecular & Cellular Neurobiology, Center for Neurogenomics and Cognitive Research, Molecular and Cellular Neurobiology, Center for Neurogenomics and Cognitive Research, Neuroscience Campus Amsterdam, VU University, Amsterdam, The Netherlands.
authors.forename: Priyanka
authors.initials: P
authors.lastname: Rao-Ruiz
authors.affiliation: Department of Molecular & Cellular Neurobiology, Center for Neurogenomics and Cognitive Research, Molecular and Cellular Neurobiology, Center for Neurogenomics and Cognitive Research, Neuroscience Campus Amsterdam, VU University, Amsterdam, The Netherlands.|INSERM U862, Neurocentre Magendie, Bordeaux, France.|Université De Bordeaux, Bordeaux, France.
authors.forename: Karen E
authors.initials: KE
authors.lastname: Carney
authors.affiliation: Department of Molecular & Cellular Neurobiology, Center for Neurogenomics and Cognitive Research, Molecular and Cellular Neurobiology, Center for Neurogenomics and Cognitive Research, Neuroscience Campus Amsterdam, VU University, Amsterdam, The Netherlands.
authors.forename: Nikhil
authors.initials: N
authors.lastname: Pandya
authors.affiliation: Department of Molecular & Cellular Neurobiology, Center for Neurogenomics and Cognitive Research, Molecular and Cellular Neurobiology, Center for Neurogenomics and Cognitive Research, Neuroscience Campus Amsterdam, VU University, Amsterdam, The Netherlands.
authors.forename: Rolinka J
authors.initials: RJ
authors.lastname: van der Loo
authors.affiliation: Department of Molecular & Cellular Neurobiology, Center for Neurogenomics and Cognitive Research, Molecular and Cellular Neurobiology, Center for Neurogenomics and Cognitive Research, Neuroscience Campus Amsterdam, VU University, Amsterdam, The Netherlands.
authors.forename: Mark H G
authors.initials: MH
authors.lastname: Verheijen
authors.affiliation: Department of Molecular & Cellular Neurobiology, Center for Neurogenomics and Cognitive Research, Molecular and Cellular Neurobiology, Center for Neurogenomics and Cognitive Research, Neuroscience Campus Amsterdam, VU University, Amsterdam, The Netherlands.
authors.forename: Pim
authors.initials: P
authors.lastname: van Nierop
authors.affiliation: Department of Molecular & Cellular Neurobiology, Center for Neurogenomics and Cognitive Research, Molecular and Cellular Neurobiology, Center for Neurogenomics and Cognitive Research, Neuroscience Campus Amsterdam, VU University, Amsterdam, The Netherlands.
authors.forename: August B
authors.initials: AB
authors.lastname: Smit
authors.affiliation: Department of Molecular & Cellular Neurobiology, Center for Neurogenomics and Cognitive Research, Molecular and Cellular Neurobiology, Center for Neurogenomics and Cognitive Research, Neuroscience Campus Amsterdam, VU University, Amsterdam, The Netherlands.
authors.forename: Sabine
authors.initials: S
authors.lastname: Spijker
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000502:physiology*; D003213:Conditioning, Psychological / Q000502:physiology*; D005239:Fear / Q000502:physiology*; D006624:Hippocampus / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D020543:Proteome / Q000378:metabolism*; D013315:Stress, Psychological / Q000378:metabolism*; D013570:Synaptic Membranes / Q000378:metabolism*; D013997:Time Factors
chemical_list: D020543:Proteome
keywords: hippocampus; iTRAQ; memory; proteomics; stress