These structural and cytoskeletal-related proteins are just a sampling of the differences detected as the synapse CC was highly enriched in the network of differential expressed proteins and phosphorylated proteins. Further work is necessary to fully characterize how the differential expression and phosphorylations of these structural and cytoskeletal-related proteins associated with the synaptic CC work in conjunction to produce the differential physiological properties of MSNs in the DS and potentially contribute to differential endophenotypes described in HAP and LAP mice. Unfortunately, we discovered no direct relationship between any single differentially expressed gene, protein, or phosphopeptide and the primary neurophysiological differences we previously observed between the selected lines. For example, higher voltage-gated Na+ channel expression in HAP mice could clearly associate with heightened excitability observed in HAP mice; although we did quantify a few peptides of some Na+ channels, the relative abundances were quite low and it is unclear if their differential expression or phosphorylation states directly relate to the differential excitability profiles of MSNs in the DS of HAP and LAP mice. It is quite probable that downstream signaling mechanisms or regulatory functions related to our findings will produce the differential neuronal excitability and neurotransmitter release phenotypes.
