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The Journal of biological chemistry
Jun 19, 2015;290 (25): 15635-15645.

Strain Differences in Presynaptic Function: PROTEOMICS, ULTRASTRUCTURE, AND PHYSIOLOGY OF HIPPOCAMPAL SYNAPSES IN DBA/2J AND C57Bl/6J MICE.

A Mariette Lenselink, Diana C Rotaru, Ka Wan Li, Pim van Nierop, Priyanka Rao-Ruiz, Maarten Loos, Roel van der Schors, Yvonne Gouwenberg, Joke Wortel, Huibert D Mansvelder, August B Smit, Sabine Spijker
Author Information
  1. A Mariette Lenselink: Departments of Molecular and Cellular Neurobiology, Center for Neurogenomics and Cognitive Research, Neuroscience Campus Amsterdam, VU University, 1081 HV Amsterdam, The Netherlands.
  2. Diana C Rotaru: 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.
  3. Ka Wan Li: Departments of Molecular and Cellular Neurobiology, Center for Neurogenomics and Cognitive Research, Neuroscience Campus Amsterdam, VU University, 1081 HV Amsterdam, The Netherlands.
  4. Pim van Nierop: Departments of Molecular and Cellular Neurobiology, Center for Neurogenomics and Cognitive Research, Neuroscience Campus Amsterdam, VU University, 1081 HV Amsterdam, The Netherlands.
  5. Priyanka Rao-Ruiz: Departments of Molecular and Cellular Neurobiology, Center for Neurogenomics and Cognitive Research, Neuroscience Campus Amsterdam, VU University, 1081 HV Amsterdam, The Netherlands.
  6. Maarten Loos: Departments of Molecular and Cellular Neurobiology, Center for Neurogenomics and Cognitive Research, Neuroscience Campus Amsterdam, VU University, 1081 HV Amsterdam, The Netherlands.
  7. Roel van der Schors: Departments of Molecular and Cellular Neurobiology, Center for Neurogenomics and Cognitive Research, Neuroscience Campus Amsterdam, VU University, 1081 HV Amsterdam, The Netherlands.
  8. Yvonne Gouwenberg: Departments of Molecular and Cellular Neurobiology, Center for Neurogenomics and Cognitive Research, Neuroscience Campus Amsterdam, VU University, 1081 HV Amsterdam, The Netherlands.
  9. Joke Wortel: Functional Genomics, Center for Neurogenomics and Cognitive Research, Neuroscience Campus Amsterdam, VU University, 1081 HV Amsterdam, The Netherlands.
  10. Huibert D Mansvelder: Integrative Neurophysiology, Center for Neurogenomics and Cognitive Research, Neuroscience Campus Amsterdam, VU University, 1081 HV Amsterdam, The Netherlands.
  11. August B Smit: Departments of Molecular and Cellular Neurobiology, Center for Neurogenomics and Cognitive Research, Neuroscience Campus Amsterdam, VU University, 1081 HV Amsterdam, The Netherlands.
  12. Sabine Spijker: 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.
PMID: 25911096 DOI: 10.1074/jbc.M114.628776

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.

Keywords

RASAL1 electrophysiology exocytosis iTRAQ neuroscience neurotransmitter release presynaptic proteomics synaptic plasticity

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MeSH Term

Animals
Cognition
Hippocampus
Memory
Mice
Mice, Inbred DBA
Nerve Tissue Proteins
Post-Synaptic Density
Proteome
Proteomics
Species Specificity

Chemicals

Nerve Tissue Proteins
Proteome
Journal Article Research Support, Non-U.S. Gov't

Word Cloud

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