Strain differences in presynaptic function: proteomics, ultrastructure and physiology of hippocampal synapses in DBA/2J and C57Bl/6J mice [Genomics and Proteomics]

April 24th, 2015 by Lenselink, A. M., Rotaru, D. C., Li, K. W., van Nierop, P., Rao-Ruiz, P., Loos, M., van der Schors, R., Gouwenberg, Y., Wortel, J., Mansvelder, H. D., Smit, A. B., Spijker, S.

The inbred strains C57BL/6J (C57) 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 post-synaptic protein expression underlying synaptic transmission and plasticity. We measured the synaptic hippocampal protein content (iTRAQ and mass spectrometry), CA1 synapse ultrastructural morphology and synaptic functioning in adult C57 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 post-synaptic differences, the change in dynamic properties of presynaptic transmitter release may underlie compromised synaptic processing related to cognitive functioning in DBA mice.
  • Posted in Journal of Biological Chemistry, Publications
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