Novel cyclic AMP signalling avenues in learning and memory

Short summary of the PhD thesis: The main focus of this study was to investigate the fundamental processes of learning and memory, with the aim of understanding the molecular mechanisms involved. It is believed that memories form in synapses, i.e. in the connections formed between neurons in the brain. So far, a large number of molecules that can modulate the strength of synaptic connections have been shown to be involved in learning and memory processes. In the current thesis, we aimed to investigate the role of two recently discovered, cAMP signalling avenues, A-kinase anchoring proteins (AKAPs) and exchange protein activated by cAMP (Epac), in memory processes. We could show that two members of the AKAP family, AKAP150 and mAKAP as well exchange protein activated by cAMP variant 2 (Epac2) are widely expressed in the mouse brain. Moreover, we could show that both AKAP150 and Epac2 play specific roles in the molecular machinery of learning and memory. Particularly, AKAP150 appeared to be important in consolidation (or storage) of emotional associative memory and in novelty processing, whereas Epac activation improved emotional memory retrieval, or memory recollection. Moreover, our data show that both AKAPs and Epac might mediate a more fine-tuned level of organization for cAMP second messenger systems. Therefore, our results yield important insights in the role of AKAPs, compartmentalized cAMP signalling and Epac in the different stages of learning and memory. In addition to the fundamental significance of understanding cAMP signalling cascades, our research opens up new routes for the development of new therapeutic strategies for memory-associated disorders and pathologies.