title: Strain Differences in Presynaptic Function: PROTEOMICS, ULTRASTRUCTURE, AND PHYSIOLOGY OF HIPPOCAMPAL SYNAPSES IN DBA/2J AND C57Bl/6J MICE.
abstract: The inbred strains C57BL/6J and DBA/2J (DBA) display striking differences in a number of behavioral tasks depending on hippocampal function, such as contextual memory. Historically, this has been explained through differences in postsynaptic protein expression underlying synaptic transmission and plasticity. We measured the synaptic hippocampal protein content (iTRAQ (Isobaric Tags for Relative and Absolute Quantitation) and mass spectrometry), CA1 synapse ultrastructural morphology, and synaptic functioning in adult C57BL/6J and DBA mice. DBA mice showed a prominent decrease in the Ras-GAP calcium-sensing protein RASAL1. Furthermore, expression of several presynaptic markers involved in exocytosis, such as syntaxin (Stx1b), Ras-related proteins (Rab3a/c), and rabphilin (Rph3a), was reduced. Ultrastructural analysis of CA1 hippocampal synapses showed a significantly lower number of synaptic vesicles and presynaptic cluster size in DBA mice, without changes in postsynaptic density or active zone. In line with this compromised presynaptic morphological and molecular phenotype in DBA mice, we found significantly lower paired-pulse facilitation and enhanced short term depression of glutamatergic synapses, indicating a difference in transmitter release and/or refilling mechanisms. Taken together, our data suggest that in addition to strain-specific postsynaptic differences, the change in dynamic properties of presynaptic transmitter release may underlie compromised synaptic processing related to cognitive functioning in DBA mice.
authors.affiliation: Departments of Molecular and Cellular Neurobiology, Center for Neurogenomics and Cognitive Research, Neuroscience Campus Amsterdam, VU University, 1081 HV Amsterdam, The Netherlands.
authors.forename: A Mariette
authors.initials: AM
authors.lastname: Lenselink
authors.affiliation: Departments of Molecular and Cellular Neurobiology, Center for Neurogenomics and Cognitive Research, Neuroscience Campus Amsterdam, VU University, 1081 HV Amsterdam, The Netherlands; Integrative Neurophysiology, Center for Neurogenomics and Cognitive Research, Neuroscience Campus Amsterdam, VU University, 1081 HV Amsterdam, The Netherlands.
authors.forename: Diana C
authors.initials: DC
authors.lastname: Rotaru
authors.affiliation: Departments of Molecular and Cellular Neurobiology, Center for Neurogenomics and Cognitive Research, Neuroscience Campus Amsterdam, VU University, 1081 HV Amsterdam, The Netherlands.
authors.forename: Ka Wan
authors.initials: KW
authors.lastname: Li
authors.affiliation: Departments of Molecular and Cellular Neurobiology, Center for Neurogenomics and Cognitive Research, Neuroscience Campus Amsterdam, VU University, 1081 HV Amsterdam, The Netherlands.
authors.forename: Pim
authors.initials: P
authors.lastname: van Nierop
authors.affiliation: Departments of Molecular and Cellular Neurobiology, Center for Neurogenomics and Cognitive Research, Neuroscience Campus Amsterdam, VU University, 1081 HV Amsterdam, The Netherlands.
authors.forename: Priyanka
authors.initials: P
authors.lastname: Rao-Ruiz
authors.affiliation: Departments of Molecular and Cellular Neurobiology, Center for Neurogenomics and Cognitive Research, Neuroscience Campus Amsterdam, VU University, 1081 HV Amsterdam, The Netherlands.
authors.forename: Maarten
authors.initials: M
authors.lastname: Loos
authors.affiliation: Departments of Molecular and Cellular Neurobiology, Center for Neurogenomics and Cognitive Research, Neuroscience Campus Amsterdam, VU University, 1081 HV Amsterdam, The Netherlands.
authors.forename: Roel
authors.initials: R
authors.lastname: van der Schors
authors.affiliation: Departments of Molecular and Cellular Neurobiology, Center for Neurogenomics and Cognitive Research, Neuroscience Campus Amsterdam, VU University, 1081 HV Amsterdam, The Netherlands.
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Gouwenberg
authors.affiliation: Functional Genomics, Center for Neurogenomics and Cognitive Research, Neuroscience Campus Amsterdam, VU University, 1081 HV Amsterdam, The Netherlands.
authors.forename: Joke
authors.initials: J
authors.lastname: Wortel
authors.affiliation: Integrative Neurophysiology, Center for Neurogenomics and Cognitive Research, Neuroscience Campus Amsterdam, VU University, 1081 HV Amsterdam, The Netherlands.
authors.forename: Huibert D
authors.initials: HD
authors.lastname: Mansvelder
authors.affiliation: Departments of Molecular and Cellular Neurobiology, Center for Neurogenomics and Cognitive Research, Neuroscience Campus Amsterdam, VU University, 1081 HV Amsterdam, The Netherlands.
authors.forename: August B
authors.initials: AB
authors.lastname: Smit
authors.affiliation: Departments of Molecular and Cellular Neurobiology, Center for Neurogenomics and Cognitive Research, Neuroscience Campus Amsterdam, VU University, 1081 HV Amsterdam, The Netherlands. Electronic address: s.spijker@vu.nl.
authors.forename: Sabine
authors.initials: S
authors.lastname: Spijker
mesh_terms: D000818:Animals; D003071:Cognition / Q000502:physiology*; D006624:Hippocampus / Q000502:physiology / Q000648:ultrastructure; D008568:Memory / Q000502:physiology*; D051379:Mice; D008811:Mice, Inbred DBA; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D057907:Post-Synaptic Density; D020543:Proteome / Q000378:metabolism* / Q000502:physiology / Q000648:ultrastructure; D040901:Proteomics; D013045:Species Specificity
chemical_list: D009419:Nerve Tissue Proteins; D020543:Proteome
keywords: RASAL1; electrophysiology; exocytosis; iTRAQ; neuroscience; neurotransmitter release; presynaptic; proteomics; synaptic plasticity