Protein expression profiling of mouse hippocampus area CA1 and CA3 during memory formation

The hippocampal formation is a brain structure essential for higher-order cognitive functions. It has a characteristic anatomical organization and cellular composition, and its sub-regions have different properties and functional roles. Areas CA1 and CA3 in particular, are key sub-regions for learning and memory formation that fulfill complementary but specific functions. The molecular basis for such specific properties and the link to learning and memory remain unknown. The work presented in this thesis analyzes protein expression differences between hippocampus area CA1 and area CA3 under basal conditions and changes in protein expression induced by two different learning paradigms. It provides evidence that there are extensive differences between the proteome of the two sub-regions. SWATH-MS is used to identify proteins with expression differences between area CA1 and area CA3 under basal conditions. It is further demonstrated that both learning paradigms induce changes in protein expression in area CA1 and area CA3 at multiple time-points following the tasks. The application of bioinformatics tools allowed us to interpret the expression data over the whole time-course and revealed intriguing differences between the two subregions. It is shown that dynamic changes in area CA1 are consistent throughout both learning paradigms. In contrast, changes induced in area CA3 by the two learning paradigms differ from each other. A more detailed analysis of area CA1 reveals a group of proteins that display similar expression characteristics in both paradigms. Members of this group are components of the electron transport chain. They show a characteristic down-regulation after two hours and up-regulation after eight hours. In the discussion we explore how these electron transport chain proteins could contribute to the role of area CA1 in episodic memory formation and what additional experiments would be necessary to demonstrate this