TY - JOUR
T1 - Strain Differences in Presynaptic Function: Proteomics, Ultrastructure, and Physiology of Hippocampal Synapses in DBA/2J AND C57Bl/6J mice..
AU - Lenselink, A.M.
AU - Rotaru-Marcu, D.C.
AU - Li, K.W.
AU - van Nierop, P.
AU - Rao-Ruiz, P.
AU - Loos, M.
AU - van der Schors, R.C.
AU - Gouwenberg, Y.
AU - Wortel, J.
AU - Mansvelder, H.D.
AU - Smit, A.B.
AU - Spijker, S.
PY - 2015
Y1 - 2015
N2 - 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.
AB - 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.
U2 - 10.1074/jbc.M114.628776
DO - 10.1074/jbc.M114.628776
M3 - Article
SN - 0021-9258
VL - 290
SP - 15635
EP - 15645
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 25
ER -