We use a combination of live cell imaging and stochastic modeling of signaling pathways to investigate how noradrenergic receptor stimulation interacts with calcium to control cAMP, required for synaptic plasticity and memory in the hippocampus. Our simulation results explain the mechanism whereby prior noradrenergic receptor stimulation does not enhance the subsequent NMDA stimulated cAMP elevation. Specifically, our results demonstrate the the negative feedback loop from cAMP, through PKA, to PDE4 cannot explain the results, and that switching of the noradrenergic receptor from Gs to Gi is required.
Chay A, Zamparo I, Koschinski A, Zaccolo M, Blackwell KT (2016) Control of ßAR- and N-methyl-D-aspartate (NMDA) Receptor-Dependent cAMP Dynamics in Hippocampal Neurons. PLoS Comput Biol 12:e1004735 [PubMed]