Molecular analysis of increased cognitive performance in Sharp1 and Sharp2 double knockout mice

Altered sleep/wake behavior as well as a decrease in cognitive performance are observed in many psychiatric diseases such as bipolar disorder and schizophrenia. The goal of my PhD thesis is to investigate the circadian regulated molecular mechanisms that finally lead to a higher performance of the learning and memory behavior and to find a strategy to target these factors. I will use Sharp-1 and -2 double knock out (S1/2^-/-) mice, because these mice display an increase of cognitive performance accompanied with altered sleep/wake patterns. It has been shown recently that cellular signaling cascades may couple learning performance differences at given circadian time points. On the molecular level it is completely unknown how the circadian cycle is connected to learning performance. By profiling potential signaling cascades I expect to identify molecular pathways that are changed in S1/2^-/- mice and finally lead to the cognitive phenotype. Respective cascade members and their appropriate receptors will be analyzed in cell biological assays and mouse experiments. The final aim is to establish an assay to detect the receptor activities of the identified altered signaling cascades in real time. I suppose that this will not only lead to a better understanding of the circadian role in psychiatric diseases, but also potentially reveal important receptors for antipsychotic drugs.